18 Apr 2017 1132198435XKBMH4XAnnexure-AdditionalAttachmentsFile

M/S. KALKI CHEMICALS INDUSTRIES. GIDC NANDESARI, VADODARA.
ANNEXURE-I
PROPOSED TERMS OF REFERENCE
 Standard TOR of MoEF&CC for organic sector will be followed.
M/s. Jyoti Om Chemical Research Centre Pvt. Ltd.11

ANNEXURE-II
COPY OF CCA






ANNEXURE-III
LIST OF EXISTING & PROPOSED PRODUCTS AND THEIR PRODUCTION CAPACITY
Sr. Product Name Existing Proposed Total

No. Quantity in Quantity in Capacity
MT/Month MT/Month MT/ Month
Existing As Per CCA No.-AWH-84183
1. Sulfonated mass (Resist salt) 850 0 850
2. Gypsum 96 154 250
3. LIS-III(L-proline benzyl Ester 15 0 15
hydrochloride)
4. CR-II 15 0 15
5. SABAM TA 50 -25 25
6. RABAN base 14.5 0 14.5
7. Research Product 5 15 20
8. Trityl Chloride 10 5 15
9. LIS-5Trifluoroacetic acid isopropyl 10 0 10
cster)
10. LIS-II(4-phenyl 2-oxobutyrate) 10 5 15
11. Ethyl trifluoroaccetate 10 5 15
12. Phenyl Ethyl chloride 15 0 15
13. Trifluoroaceticacid 50 20 70
Total 1150.5 179 1329.5
Proposed
Sr. Name of Product Existing Proposed Total
1. S-2-Aminobutyramide Hydrochloride 0 50 50
(SABAM HCl)
2.. Cyano Acetic Acid 0 15 15
3. Isopropyl Trifluoroacetate - Route 1 0 100 100
&2
4. Ethyl Trifluoroacetate Route 1 & 2 0 15 15
5. DL-Mandelic - Route 1 0 30 30
6. Trifluoroacetyl L-Lysine 0 25 25
7. 4-Bromo Phenyl Acetic Acid 0 15 15
8. 4-Bromo Benzyl Cyanide 0 15 15
9. Choline Chloride 0 50 50
10. 4-Nitro 1H-imidazole (LARM-61) 0 15 15
11. 2-chloro ethyl morpholine HCl 0 15 15

(LARM-62)
12 ANCP 0 15 15


13. ANFP 0 15 15
14. Diketone 0 25 25
15. 3-CTMPP (3-(2-chloroethyl)-2- 0
methyl-4-oxo-6,7,8,9-tetrahydro-4H-
pyrido[1,2-a]pyrimidin-1-ium
chloride) 25 25
16. Phenylglycine 0 30 30
17. Venlafaxine stage 1 & 2 0 15 15
18. 5-Nitroisophthalic Acid Dimethyl 0
Ester (XR-202) 60 60
19. 5-Nitroisophthalic Acid Methyl Ester 0
(XR-201) 50 50
20. P-Sulfonyl benzoic acid potassium 0
salt (SB-201) 50 50
21. DS-201(5-Chlro-2,3-Disulfonamide 0
Aniline) 50 50
22. 3-amino-1,2-propanediol (AP-301) 0 100 100
23. NM Base 0 50 50
24. T1(1-(3-Chlorophenyl)Piperazine) 0 15 15
25. (1-(3-chlorophenyl)-4-(3- 0 15 15
chloropropyl) piperazine (T2)
hydrochloride)
26. Dione-celecoxib 0 15 15
27. Ethyl 2-(4-hydroxyphenyl)-4- 0
methylthiazole-5-carboxylate(FB1) 24 24
28. FBT(Ethyl-2-(3-Cyano-4- 0
isobutoxyphenyl)-4-methyl-1,3-
thiazole-5-carboxylate) 12 12
29. exo,exo-2,3-camphanediol(CDO) 0 5 5
30. 3-Ethyl-4-methyl-pyrolidine-2-one 0
(GP1) 10 10
31. Adrenaline (ADIF) 0 10 10
32. Trans-4-aminocyclohexanol 0 20 20
33. Isoproternol (ISL) 0 20 20
34. QuetiapineFumarate 0 5 5
35. Minodronic Acid 0 2 2
36. Nisoldipine 0 2 2
37. Metaxalon 0 2 2
38. Agomelatine 0 2 2
39. Iloperidone 0 2 2
40. Febuxostate 0 2 2
41. Warfarin Sodium 0 5 5


42. Mexiletine Hydrochloride 0 2 2
43. Felodipine 0 2 2
44. Clopidogrel Bisulfate 0 2 2
45. Rabepzole Sodium/Sulphate 0 2 2
46. Celecoxib 0 10 10
47. Derifenacin 0 2 2
48. Etoricoxib 0 2 2
49. MemantineHcl 0 2 2
50. Pregabalin 0 2 2
51. Famotidine 0 2 2
52. Ivabradine 0 2 2
53. Levitracetam 0 2 2
54. Valsartan 0 2 2
55. Irbesartan 0 2 2
56 Fenofibrate 0 10 10
57. Venlafaxine 0 10 10
58. Amlodipine Besylate 0 2 2
59. Trazodone Hydrochloride 0 2 2
60. Paracetamol 0 90 90
61. Azilsartan 0 2 2
Total 0 1150 1150
TOTAL(Existing +Proposed) 1150.5 1329 2479.5

ANNEXURE-IV
LIST OF PROPRIETOR
Sr. Name Of Residential Address Mobile No.

No. PROPRIETOR
1. Mr. 11,Goverdhan society
942611906
PrakashJ.Vakharia Nizampura,Vadodara-2

ANNEXURE-V
PLANT LAYOUT

ANNEXURE-VI
LIST OF PROPOSED RAW MATERIALS
Sr. Name of Product Production Name of Raw material Raw

No. quantity in Raw material consumption material
MT/Month quantity in consumption
MT/T quantity in
MT/Month
1 Trifluoroacetic Acid 70 TFA ML (28%
TFA in Water) 4.5 315
Soda Ash 0.48 33.6
Sulphuric Acid 3.5 245
Dil Sulphuric
Acid 5.28 369.6
Calcium
Hydroxide 1 70
Total 14.76 1033.2
2. Phenyl Ethyl Chloride 15 Thionyl
Chloride 1.03 15.45
Phenyl Ethyl
Alcohol 0.93 13.95
10%NaOH
Solution 10 150
Total 11.96 179.4
3. LIS-III (L-Proline Benzyl 15
Ester Hydrochloride) Dichlorometha
ne 0.5 7.5
L-Proline 0.6 9
Benzyl Alcohol 1.68 25.2
Fresh Ethyl
Acetate 0.5 7.5
NaCl 1.2 18
Fresh
Sulphuric Acid 1 15
10% NaOH
Solution 6 90
Total 11.48 172.2
4. CR-II 15
Dichlorometha
ne 0.3 4.5
Thiazole Ester 0.1 1.5
Trityl Chloride 0.57 8.55
Catalyst 0.04 0.6


MT/T quantity in
MT/Month
Methanol 0.5 7.5
NaOH Flakes 1.65 24.75
Total 3.16 47.4
5. S-2- 25 ACH 1.46 36.5
AminobutyramideTartarate Propanaldehyd
(SABAM TA) e 1 25
Catalyst 0.24 6
Ammonia 0.42 10.5
NaOH 0.14 3.5
Methanol 1.5 37.5
Tartaric Acid 0.53 13.25
Total 5.29 132.25
6. S-2-Aminobutyramide 50 SABAM-TA 1.75 87.5
Hydrochloride (SABAM Fresh
HCl) Methanol 0.25 12.5
Ammonia Gas 0.2 10
Fresh IPA 0.25 12.5
NaCl 1.6 80
Fresh
Total 5.39 269.5
7. Cyano Acetic Acid 15 Monochloroace
tic acid 1.25 18.75
Sodium
Carbonate 0.725 10.875
Sodium
Cyanide 0.735 11.025
HCl (28%) 1.75 26.25
Total 4.46 66.9
8. Isopropyl Trifluoroacetate 100 Trifluoroacetic
Route-I Acid 0.81 81
Isopropyl
Alcohol 0.43 43
Resin 0.1 10
Total 1.34 134
8. Isopropyl Trifluoroacetate Trifluoroacetic
Route-II Acid 0.81 81
Isopropyl
Alcohol 0.43 43


MT/T quantity in
MT/Month
Calcium
Hydroxide 0.23 23
Total 1.57 157
9. Ethyl Trifluoroacetate 15 Trifluoroacetic
Route-I Acid 0.84 12.6
Ethanol 0.34 5.1
Fresh resin 0.01 0.15
Total 1.19 17.85
9 Ethyl Trifluoroacetate Trifluoroacetic
Route-II Acid 0.89 13.35
Ethanol 0.36 5.4
Sulphuric Acid 0.05 0.75
Calcium
Hydroxide 0.15 2.25
Total 1.45 21.75
10. DL-Mandelic Acid 30 Benzaldehyde 0.85 25.5
Sodium
Bisulphite
Solution (40%) 1.4 42
Sodium
Cyanide 0.64 19.2
HCl Solution
(28%) 0.57 17.1
Fresh DCM 0.63 18.9
Total 4.09 122.7
11. Trifluoroacetyl L-Lysine 25 Catalyst 0.1 2.5
L-Lysine 0.69 17.25
TFAE 0.65 16.25
NaCl 0.86 21.5
28% HCl
Solution 0.05 1.25
Total 2 59
12. (Ethyl-4-phenyl-2- 25 Tetrahydrofura
oxobutyrate (LIS-II) n 1 25
Magnesium
Turnings 0.14 3.5
Catalyst 0.03 0.75
Phenyl Ethyl
Chloride 0.72 18
Fresh Diethyl 0.9 22.5


MT/T quantity in
MT/Month
Oxalate
Aq. HCl(10%) 2 50
Total 5 120
13. Trityl Chloride 15 Trityl Alcohol 1.5 22.5
Fresh Methanol 0.5 7.5
Fresh Toluene 0.23 3.45
Nacl 0.8 12
40% NaOH
Solution 0.93 13.95
Total 4.65 69.75
14. 4-Bromo Phenyl Acetic Acid 15 4-Bromobenzyl
cyanide 1.25 18.75
48% Aq.
NaOH 1.2 18
Aq. HCl (28%) 1.88 28.2
Total 4.33 64.95
15. 4-Bromo Benzyl Cyanide 15 4-
Bromotoluene 0.85 12.75
Chlorobenzene 0.5 7.5
Catalyst A 0.06 0.9
Bromine
Liquid 1.1 16.5
10% Aq.
Na2CO3 1.5 22.5
Catalyst B 0.06 0.9
NaCN 1 12
Total 5 73
16. Choline Chloride 50 30%
Triethylamine
Solution 1.56 78
Ethylene Oxide 0.36 18
28% HCl 1.05 52.5
Total 3 149
17. 4-Nitro 1H-imidazole 15 Imidazole 0.75 11.25
(LARM-61) H2SO4 1.24 18.6
Oleum (65%) 1.8 27
Fuming HNO3 0.66 9.9
Total 4 67
18. 2-chloro ethyl 15 Hydroxy ethyl 0.89 13.35


MT/T quantity in
MT/Month
morpholineHCl (LARM-62) Morpholine
Thionyl
chloride 0.93 13.95
Fresh Ethylene
dichloride 0.25 3.75
40%NaOH
Solution 1.55 23.25
Total 4 54
19. ANCP 15 2,6 -Dichloro
pyridine 0.84 12.6
Fuming HNO3 0.72 10.8
Con. H2SO4 1.25 18.75
Fresh IPA 0.32 4.8
Liq. Ammonia 1 15
Total 4 62
20. ANFP 15 ANCP 0.67 10.05
4-Fluoro
benzyl amine 0.51 7.65
Sodium
carbonate 0.41 6.15
Total 1.59 23.85
21. Diketone 25 Methanol 0.1 2.5
Sodium
Methoxide 0.25 6.25
Isopropyl
Trifluoroacetat
e 0.71 17.75
4-methyl
Acetophenone 0.58 14.5
Acetic Acid 0.13 3.25
Total 2 44
22. 3-CTMPP (3-(2- 25 2-
chloroethyl)-2-methyl-4- Aminopyridine 0.74 18.5
oxo-6,7,8,9-tetrahydro-4H- 2-
pyrido[1,2-a]pyrimidin-1- acetylbutyrolac
ium chloride) tone 1.01 25.25
Dichlorometha
ne 0.06 1.5
Aq. 1.41 35.25


MT/T quantity in
MT/Month
NaOH(20%)
Phosphorous
Oxychloride 1.33 33.25
Methanol 0.34 8.5
Fresh Pd/C 0.01 0.25
Charcoal 0.04 1
Celite 0.02 0.5
Conc. HCl 0.3 7.5
Total 5 132
23. Phenylglycine 30 Benzaldehyde 0.74 22.2
Sodium
cyanide 0.3 9
Ammonium
carbonate 0.15 4.5
Methanol 0.06 1.8
Caustic Lye 0.5 15
Total 1.95 58.5
24. Venlafaxine stage 1 & 2 15 Cyclohexanone 0.6 9
4MEP 0.7 10.5
KOH 0.1 1.5
Raney Ni 0.02 0.3
Hydrogen 0.07 1.05
Total 1.88 28.2
25. 5-Nitroisophthalic Acid 60 XR-101(5-nitro
Dimethyl Ester (XR-202) isophathalic
acid) 0.85 51
Fresh Methanol 0.5 30
Sulphuric 0.2 12
Total 2 93
26. 5-Nitroisophthalic Acid 50 XR-101(5-nitro
Methyl Ester (XR-201) isophathalic
acid) 1.75 87.5
Fresh Toluene 0.5 25
Sodium
Bicarbonate 0.2 10
conc. HCl 0.15 7.5
Total 3 140


MT/T quantity in
MT/Month
27. P-Sulfonyl benzoic acid 50 SB-101 1.0 47.5
potassium salt (SB-201) KMnO4 0.3 15.0
KOH 0.1 2.5
conc. HCl 0.2 7.5
Total 1.5 72.5
28. 5-Chlro-2,3-Disulfonamide 50 DS-201 Crude 1.10 55.0
Aniline (DS-201) Caustic Lye 0.30 15.0
Total 1.55 77.5
29. 3-amino-1,2-propanediol 100 EPC 1.20 120
(AP-301) sulphuric acid 0.05 5
cesium
carbonate 0.01 1
Fresh
Ammonia 0.20 20
Total 1.46 146
30. NM Base 50 CMN 1.20 60
MMA 0.20 10
Methanol 0.20 10
Total 1.60 80
31. T1(1-(3- 15 MCA 0.7 10.5
Chlorophenyl)Piperazine) Toluene 0.5 7.5
Bis-2-chloro 1.0 14.3
Caustic Lye 1.0 15.0
Total 3.2 47.3
32. 1-(3-chlorophenyl)-4-(3- 15 T1 0.5 7.5
chloropropyl) piperazine Acetone 0.3 4.5
(T2) hydrochloride Caustic Lye 0.3 4.5
CBP 0.6 9.0
Total 1.7 25.5
33. CXB Dione& 4-[5-(4- 15 4MAP 0.5 7.5
methylphenyl)-3- ETA 0.6 9.0
(trifluoromethyl)pyrazol-1- Sodium
yl]benzenesulfonamide Methoxide 0.3 4.5
Methanol 0.6 9.0
con. HCl 0.1 1.5
Total 2.1 31.5
34. Ethyl 2-(4-hydroxyphenyl)- 24 Fresh DMF 0.3 7.2
4-methylthiazole-5- Pcp 0.5 12.0
carboxylate(FB1) Sodium 0.6 14.4


MT/T quantity in
MT/Month
Sulphide
E2caa 0.5 12.0
Total 2.4 57.6
35. FBT(Ethyl-2-(3-Cyano-4- 10 FB1 1.2 12
isobutoxyphenyl)-4-methyl- MSA 2.0 20
1,3-thiazole-5-carboxylate) HEXAMINE 0.5 5
Fresh
TOLUENE 0.5 5
Fresh DMF 0.5 5
IBB 0.5 5
K2CO3 0.3 3
Methanol 0.2 2
Thionyl
Chloride 0.1 1
Hydroxylamine
HCl 0.5 5
Total 6.3 63
36. Exo,exo-2,3- 5 Camphorquino
camphanediol(CDO) ne 1.03 5.15
Ether 0.10 0.5
Lithium
Aluminium
Hydride 0.30 1.5
Dilute HCl
(10%) 1 5
Total 2.43 12.15
37. 3-Ethyl-4-methyl-pyrolidine- 10 Ethyl
2-one (GP1) Acetoacetate 1.5 15.3
Ethyl Bromide 0.6 6.0
Sodium
Methoxide 1.0 10.0
sodium
bisulfite 0.5 5.0
sodium cyanide 0.3 3.0
sulphuric acid 0.3 2.5
Raney Nickel 0.1 1.0
Thionyl 0.2 1.5


MT/T quantity in
MT/Month
Chloride
Hydrogen Gas 0.3 2.5
Soda Ash 0.3 3.0
Total 5.5 54.8
38. Adrenaline (ADIF) 10 Adrenalone 1.1 11.2
Fresh THF 0.3 2.5
Lithium
Aluminium
Hydride 0.4 4.0
Toluene 0.1 1.0
Total 2.2 21.7
39. Trans-4-Aminocyclohexanol 20 Paracetamol 1.0 20
Fresh Rhodium 0.1 1
Hydrogen 0.3 6
Caustic Lye 0.3 6
Fresh Methanol 0.1 2
Total 1.8 35
40. Isoproternol (ISL) 20 Chloroacetyl
Catechol 1.1 22.4
Isopropyl
amine 0.5 10
Hydrochloric
acid 0.6 12
Total 2.3 45
41. QuetiapineFumarate 5 Dibenzo 0.6 3
phosphorous
oxychloride 0.5 2.5
Fresh Triethyl
Amine 0.01 0.1
Caustic Lye 0.3 1.5
HEEP 0.4 1.9
Soda Ash 0.3 1.5
Furmaric Acid 0.2 0.8
Total 2.4 11.8
42. Minodronic Acid 2 2 Amino
Pyridine 0.5 1.1
Chloro 1 2


MT/T quantity in
MT/Month
Acetaldehyde
Sodium
Bicarbonate
Solution 1.5 3.0
Ethyl Oxalyl
Chloride 1.5 3.0
Potassium
Hydroxide 0.3 0.5
Hydrochloric
Acid 1.3 2.5
PCL3 2.8 5.5
Total 8.8 17.5
43. Nisoldipine 2 2-
Nitrobenzaldeh
yde 0.63 1.25
Isobutyl
Acetoacetate 0.62 1.24
2-
Nitrobenzylidin
e Aceto acetic
acid Isobutyl
Ester 1.20 2.41
Methyl-3-
Amino
Crotonate 0.71 1.43
Total 3.16 6.33
44. Metaxalon 2 3,5-
Dimethylpheno
l 1.8 3.7
Epichlorohydri
ne 1.4 2.8
Aq. Potassium
Hydroxide 1.0 2.1
Ethyl
Carbamate 0.9 1.7
Triethyl Amine 0.2 0.4
Total 5.3 10.6
45. Agomelatine 2-(7-methoxy-
1-
napthyl)Aceton
itrile 2.5 4.9


MT/T quantity in
MT/Month
Fresh Isopropyl
Alcoho HCl 0.2 0.4
Anhydrous
Sodium
Acetate 0.5 1.0
FreshAnhydrou
s Acetic 0.1 0.2
Total 3.3 6.7
46. Iloperidone 2 4 Methoxy-3-
hydroxy
1-Bromo-3-
Choloropropan
e 1.0 2.1
Potassium
Carbonate 1.0 1.9
6-Fluoro-3-(4-
piperidinyl)-
1,2-
benzisoxazole
hydrochloride 0.8 1.5
Sodium
Bromide 0.3 0.6
Total 3.6 7.2
47. Febuxostate 2 Ethyl 2-(4-
hydroxyphenyl
)-4-
methylthiazole-
5-carboxylate 1.10 2.20
Caustic Flakes 1.84 3.68
Carbon 0.02 0.04
Total 3.68 7.36
48. Warfarin Sodium 2 2-Hydroxy
Diethyl
Carbonate 1.00 2.00
Sodium 0.76 1.52


MT/T quantity in
MT/Month
Methoxide
Benzal
Acetone 0.69 1.39
Triethylamine 0.05 0.09
Total 3.27 6.54
49. Mexiletine Hydrochloride 2 2-phenyl
ethanol 0.8 1.6
Epichlorohydri
ne 0.6 1.3
Potasium
Carbonate 1.1 2.1
Potassium
Iodide 0.1 0.1
Hydroxylamine
Hydrochloride 0.7 1.3
Sodium
Carbonate 1.4 2.8
Total 4.8 9.7
50. Felodipine 2 2,3 Dichloro
Benzaldehyde 0.67 1.34
Methyl Aceto
Acetate 0.47 0.94
3-Amino
Cotonic acid
Ethyl ester 0.63 1.26
Total 1.77 3.54
51. Clopidogrel Bisulfate 3 DL-2-
cholorophenyl
glycine 2.14 6.42
Thionyl
Chloride 1.00 3.00
Methanol 1.26 3.78
Sodium
Bicarbonate
Solution 3.36 10.08
Triethyl amine 1.98 5.94
p- toluene
Sulphonyl 0.78 2.34


MT/T quantity in
MT/Month
chloride
Sodium
Bicarbonate 1.83 5.49
Dipotassium
hydrogen
sulphate 1.51 4.53
2-Thienylethyl
para-toluene
sulphonate 1.59 4.77
Hydrochloric
Acid 0.65 1.95
Aq.Formaldehy
de 1.35 4.05
Total 18.72 56.16
52. Rabepzole Sodium 2 RAB/Hydroxy 1.10 2.20
Thionyl
Chloride 0.64 1.28
2-Mercepto
Benzimidazole 0.65 1.30
Sodium
Hydroxide 0.49 0.98
Sodium
Hypochloride 4.05 8.10
Sodium
Hydroxide 0.81 1.62
Total 7.74 15.48
53. Celecoxib 10 CXB Dione 1.22 12.2
Sulfonamide 0.44 4.4
Total 1.96 19.6
54. Derifenacin 2 KSM I 2.3 4.6
Sodium
Hydroxide 0.6 1.1
KSM II 0.8 1.5
Potassium
Carbonate 2.3 4.6
Hydrogen 0.3 0.6


MT/T quantity in
MT/Month
Bromide
Total 7.4 14.9
55. Etoricoxib 2 Acetic Acid 2.20 4.40
Fresh Acetone 0.05 0.10
Ammonia
Solutionb 11.00 22.00
CPT-Phosphate 2.52 5.04
Hydroxylamine
Hyflo 0.12 0.24
Fresh IPA 0.41 0.82
Ketosulfone 1.50 3.00
Potassium
0.66 1.32
Tetrabutoxide
Sodium
0.30 0.60
Acetate
Sodium
3.15 6.30
Hydroxide
Activated
0.02 0.04
Charcoal
Hexane 0.26 0.52
Hyflo 0.05 0.10
Fresh IPA 0.82 1.64
Total 25.59 51.18
56. Memantine HCl 2 1-Bromo-3,5-
Dimethyladam
antane 2.36 4.72
Acetonitrile 2.36 4.72
Polyethene
Glycol 0.11 0.22
Sodium
Hydroxide 0.03 0.06
Activated
Charcoal 0.07 0.14
Hyflo 0.10 0.20
Isopropyl
Alcohol 1.53 3.06


MT/T quantity in
MT/Month
Total 11.28 22.56
57. Pregabalin 2 Sodium
Hydroxide 1.90 3.80
4‐CMH 1.37 2.74
Liquid
Bromine 1.23 2.45
Activated
carbon 0.07 0.14
Hyflo 0.02 0.03
Hydrochloric
acid 2.46 4.92
IPA 0.83 1.66
Total 7.87 15.74
58. Famotidine 2 ITU 1.50 3.00
IF 1.15 2.30
Caustic Lye 2.50 5.00
Methanol 0.58 1.16
Ammonia 0.35 0.70
Acetic Acid 0.24 0.48
Charcoal 0.03 0.06
Hyflo 0.02 0.04
Total 6.37 12.74
59. Ivabradine 2 1,3‐Dihydro‐7,
8-
dimethoxy‐2H‐
3,3 Benzazapin 0.87 1.74
Potassium
tertButoxide 0.90 1.80
1‐Bromo‐3‐Chl
oro propane 0.84 1.68
Pd/C 0.05 0.10
DNS 0.15 0.30
KSM II 0.32 0.64
Potassium
Carbonate 0.55 1.10
sodium Iodide 0.10 0.20
Hydrochloric
Acid 0.60 1.20
Methanol 0.05 0.10


MT/T quantity in
MT/Month
Acetone 0.05 0.10
Total 4.73 9.46
60. Levitracetam 2 SABAM HCl 1.15 2.30
4CBC 1.44 2.88
KOH 2.50 5.00
MDC 0.30 0.60
Sodium
Sulphate 0.50 1.00
Ethyl Acetate 0.15 0.30
Total 6.04 12.08
61. Valsartan 2 Acetone 1.0 2.0
Hyflow 0.1 0.1
TBAB 0.0 0.0
Bromine 0.1 0.1
Carbon 0.1 0.2
Sodium
Bicarbonate 2.0 4.0
Sodium
Chloride 0.4 0.9
Valeroyl
Chloride 0.6 1.2
Sodium Azide 0.7 1.3
Sodium
Hydroxide 0.8 1.7
Hydrochloric
Acid 1.2 2.4
Biphenyl
Valine 1.4 2.9
Potassium
Carbonate 1.7 3.3
Fresh Tri-n-
butyl tin
chloride 0.1 0.2
Fresh o-xylene 0.4 0.7
Fresh
dichloromethan
e 1.0 2.0
Total 11.6 23.1
62. Irbesartan 2 Acetone 0.2 0.5
Sodium 0.3 0.5


MT/T quantity in
MT/Month
Chloride
Sodium
Hydroxide 0.7 1.3
BHD 1.1 2.3
4-BMCP 1.3 2.6
HCl 0.7 1.4
Methy t-butyl
ether 0.1 0.2
Sodium azide 0.5 1.1
sodium
hydroxide 0.2 0.4
sodium nitrate 0.2 0.4
toluene 0.2 0.4
Triethyl amine
hydrochloride 1.8 3.5
Total 7.3 14.5
63. Fenofibrate (4-
chlorophenyl)(
4-
hydroxyphenyl
)
Benzophenone 1.1 10.5
Acetone 0.4 4.0
Caustic Flakes 0.3 2.5
Chloroform 0.6 6.0
Isopropyl
Alcohol 0.5 4.8
Total 3.1 30.8
64. Venlafaxine - 1-[2- 10 IPA 0.3 2.5
(dimethylamino)-1-(4- MDC 0.3 2.5
methoxyphenyl)ethyl]cycloh Formaldehyde 0.2 2.0
exan-1-ol Formic Acid 0.2 2.0
Venelafaxine
Stage II 1.3 12.5
Total 2.2 21.5
65. Amlodipine Besylate 2 Ethyl 4-[2-(1,3-
dioxo-1,3-
dihydro-
2Hisoindol-2- 1.24 2.48


MT/T quantity in
MT/Month
yl)ethoxy]-3-
oxobutanoate(E
PEA)
2- chloro
benzaldehyde 0.85 1.70
Methyl(2E)-3-
aminobut-2-
enoate 2.23 4.46
Toluene 0.13 0.26
Acetic acid 0.60 1.20
Methylamine 1.55 3.10
Benzene
sulfonic acid 0.30 0.60
Denatured
Spirit 0.50 1.00
Total 7.52 15.04
66. Trazodone Hydrochloride 2 TZP 0.84 1.68
T2
Methanol 0.30 0.60
Potassium
Carbonate 0.28 0.56
Fresh IPA 0.15 0.30
Methanol 0.19 0.38
Total 2.61 5.22

ANNEXURE-VII
BRIEF MANUFACTURING PROCESS
Details of manufacturing process & Chemical Reaction & Material balance:
1. Trifluoroacetic Acid
Process Description:
To an SS reactor is added TFA ML. To this is added Na2CO3 and pH adjusted to 7-8. After this,
the water is removed from the reaction mass. Once this is complete, the reaction mass is
transferred to a glass lined reactor. On transferring, concentrate sulphuric acid is added and the
first cut of TFA (azeotropic of TFA and water) are distilled off. This is then taken into another
glass lined reactor and some more sulphuric acid is charged. The product is then finally distilled
out at a temperature of 70-72°C. The residual sulphuric acid is then recycled in the first cut.
Chemical Reaction:

Material Balance:
Input Reactor Output
Compound Qty (KGS) Compound Qty (KGS)
TFA ML (28% TFA in Water) 450 CO2 Gas Released 20
Soda Ash 48 SS Reactor Efflent 225
Reaction Mass 253
498 498

Reaction Mass 253 Reaction mass 150
Sulphuric Acid 105 Glass Lined Distillation Loss (First Cut) 5
First Cut Residue (Dil.
Second Cut Residue 145 Reactor Sulphuric Acid + Sodium 348
Sulphate)
503 503

Reaction mass 150 Glass Lined Final Product 100
Sulphuric Acid 100 Distillation Loss (First Cut) 5
Reactor Second Cut Residue 145
250 250

Dil Sulphuric Acid 528 Gypsum 180
Calcium Hydroxide 100 ETP Sodium Sulphate 65
Effluent (Water) 383
628 628
2. Phenyl Ethyl Chloride
Process description:
To a glass lined reactor, is charged thinly Chloride. To this is added phenyl ethyl alcohol slowly
at 0-5°C. On completion of reaction, the reaction mass is slowly heated to 100°C. The evolved
SO2 gas is scrubbed in a scrubber. Once all the unreacted thinly chloride is recovered, the
reaction mass is transferred to another glass lined reactor to carry out distillation under vacuum.
The final product is distilled under reduced pressure at 100-105°C.

Chemical Reaction:
Material Balance:
Input Output
Thionyl Chloride 103 Glass Lined SO2 Gas Released 54
Phenyl Ethyl Alcohol 93 HCl Gas Released 31
Reactor Reaction Mass 111
Total 196 Total 196

Reaction Mass 111 Glass Lined Phenyl Ethyl Chloride 100
Distillation Loss 2
Reactor Residue 9
Total 111 Total 111

SO2 Gas 54 Sodium Sulphite 106
HCl Gas 31 Scrubber Sodium Chloride 49
10%NaOH Solution 1000 Water (Effluent) 930
Total 1085 Total 1085
3. LIS-III (L-Proline Benzyl Ester Hydrochloride)
Dichloromethane is charged in a glass lined reactor. To this is added L-Proline. The reaction
mixture is stirred and refluxed. To the reaction mixture is added benzyl alcohol slowly over a
period of 40 hours and HCl gas is sparged into the reaction mass during the process. After 40
hours, the reaction is monitored on TLC. On completion, the MDC is distilled off under reduced
pressure. Meanwhile, in another glass lined reactor, ethyl acetate is precooled and the reaction
mass is slowly dumped into it. The product is then centrifuged, dried and packed.

Chemical Reaction:
Material Balance:

Fresh Dichloromethane 50 Effluent 12
Recovered Dichloromethane 550 Glass Lined Recovered Dichloromethane 550
L-Proline 60 Distillation Loss Of DCM 50
Benzyl Alcohol 168 Reactor HCl Gas 55
Dry HCl Gas (From Generator) 75 Reaction Mass 236
Total 903 Total 903

Reaction Mass 236 Glass Lined LIS-III 100
Fresh Ethyl Acetate 50 Mother Liquor 686
Recover Ethyl Acetate 500 Reactor Total 786
Total 786

Mother Liquor 686 Ethyl Acetate 500
Glass Lined
Residue 186
Reactor
Total 686 Total 686

NaCl 120 Dry HCl Gas 75
Fresh Sulphuric Acid 100 HCl Gas Sodium Sulphate 145
Generator Spent Sulphuric Acid 100
Recover Sulphuric Acid 100
Total 320 320

HCl Gas 55 Sodium Chloride 88
10% NaOH Solution 600 Scrubber Water (Effluent) 567
Total 655 Total 655

3. CR-II
Dichloromethane is charged in an SS reactor. To this thiazole ester is charged followed by

catalyst and Trityl Chloride (CRP-I). The reaction is then refluxed for 4 hours and then
monitored by HPLC. Once the reaction complies, the reaction mass is cooled and more MDC is
temperature and the mixture is refluxed till the reaction is over. End point is added followed by
the addition of HCL solution. The organic layer is separated and washed with DM water. To the
organic layer is then added Methanol and Na2CO3. The reaction mixture is refluxed for 2 hours
and then monitored by HPLC. Once the reaction is complete, the solvent (MDC +Methanol) are
distilled off to a specific volume. On completion, the reaction mass is cooled, product filtered
and dried in an RVD.
Chemical Reaction:

Material Balance:

Fresh Dichloromethane 30 Reaction Mass 567
Recovered Dichloromethane 390
Fresh Thiazole Ester 10

SS Reactor
Recovered Thiazole Ester 38
Fresh Trityl Chloride 57

Recovered Trityl Chloride 38
Catalyst 4
Total 567 Total 567

Reaction Mass 567 Reaction Mass (Organic Layer) 525
DM Water 136 Aqueous Layer 178
SS Reactor
Total 703 Total 703

Reaction Mass 525 Recovered MDC 390
Fresh Methanol 50 Recovered Methanol 200
Recvered Methanol 200 SS Reactor CR-II 100
NaOH Flakes 15 Distillation loss 25
Effluent 75
Total 790 Total 790

Aqueous Layer 178 Triethyl Amine 38
NaOH Flakes 150 Water (Effluent) 290
TEA Recovery
Total 328 Total 328
4. S-2-AminobutyramideTartarate (SABAM TA)
To an SS reactor is charged ACH. To this is added catalyst. To this is then added

propanaldehyde. The acetone is then removed from the reaction mass under reduced pressure.
On completion of recovery of acetone, to the reaction mass is added ammonia. This is then
followed by addition of dil. NaOH solution. After reaction is complete, the reaction is subjected
to water recovery under reduced pressure. On completion of water recovery, methanol is added
to the reaction mass. The salt that is precipitated is filtered and more methanols are added to the

reaction mass. This is followed by addition of tartaric acid to the reaction mass. The product is
precipitated and filtered followed by drying. The mother liquor is sent for recovery of methanol.
Chemical Reaction:

Material Balance:
Input Output
ACH 146 Acetone 90
Propanaldehyde 100 Distillation Loss 5
Catalyst 24
SS Reactor Reaction Mass 175
270 270

Reaction Mass 175 Recovered Water 120
Ammonia 42 Distillation Loss Of Water 30
NaOH 14 SS Reactor Salt 15
Methanol 150 Reaction Mass 216
381 381

Reaction Mass 216 SABAM-TA 100
Methanol 400 Methanol Reflux Loss 10
SS Reactor
Tartaric Acid 53 Mother Liquor 559
669 669

Mother Liquor 559 Methanol Recovered Methanol 400
Methanol Distillation Loss 20
Recovery Solid Residue 139
559 559
5. S-2-Aminobutyramide Hydrochloride (SABAM HCl)
To an SS reactor is charged SABAM-TA. To this is added methanol and chilled to 5-10°C. To

this is then added ammonia gas. On completion of reaction, the reaction mass is filtered and the
by-product (Di-ammonium tartarate) is filtered out and washed with methanol. The combined
mother liquor is then added to a glass lined reactor and distillation is carried out to completely
remove methanol. On complete removal of methanol, IPA-HCl is then added to the reaction
mass. The product gets precipitated and is filtered off and washed with IPA. The IPA is then
recovered and reused. The product is filtered and dried.

Chemical Reaction:

Material Balance:

SABAM-TA 175 Diammonium Tartarate 100
Fresh Methanol 25 Reaction Mass 1495
Recover methanol 1375
SS Reactor
Ammonia Gas 20
Total 1595 1595

Reaction Mass 1495 Recovered Methanol 1375
Methanol Distillation Loss Of Methanol 25
Reaction Mass 95
Recovery
Total 1495 1495

Reaction Mass 95 SABAM-HCl 100
IPA-HCl (20%) 500 GLR Reactor Mother Liquor 495
Total 595 595

Fresh IPA 25 IPA-HCl IPA-HCl 500
Recovered IPA 375
Dry HCl Gas 100 Generator
Total 500 500

Mother Liquor 495 Recovered IPA 375
IPA Recovery HCl Gas 5
Residue 115
Total 495 495

NaCl 160 HCl Gas Dry HCl Gas 100
Fresh Sulphuric Acid 134 Sodium Sulphate 194
Recovered Sulphric acid 66 Generator Spent Sulphuric Acid 66
Total 360 360
6. Cyano Acetic Acid
To a glass lined reactor is charged D.M. Water. To this, mono chloro acetic acid is charged. The
reaction mass is then neutralized with Soda Ash. To this is added an aqueous solution of sodium
cyanide. The addition is completed between 50-95°C. Once the addition is completed, the
reaction mass is refluxed for two hours. To this is added aqueous HCl solution. On the
completion of acidification, the water is removed from the reaction mass under reduced
pressure to completely remove. The product is then distilled under reduced pressure to afford
the pure product.
Chemical Reaction:
Material Balance:
Input Output
Monochloroacetic acid 125 Cyano Acetic Acid 100
Water 250 Effluent 350
Sodium Carbonate 72.5 Distillation Loss Of Water 26
Sodium Cyanide 73.5
GLR Reactor CO2 Gas 30
HCl (28%) 175 Distillation Residue 190
Total 696 Total 696
7. Isopropyl Trifluoroacetate Route-1 & Route-2 (LIS-5)
In a glass lined reactor, is charged trifluoro acetic acid and cooled to 5-15°C. To this is added
isopropyl alcohol at 5-15°C. On completion of addition, resin is added to the reaction mass. The
reaction mass is refluxed continuously to azeo tropically distill out water. The water is removed
from the reaction mass and the final product is then distilled, collected and packed in drums.
Chemical Reaction:
Reaction Scheme 1:

Reaction Scheme 2:
Material Balance:
Input Output
Trifluoroacetic Acid 81 Isopropyl Trifluoroacetate 100
Isopropyl Alcohol 43 Effluent 13
Resin 10 Glass Lined Distillation Residue 15
Reactor Distillation Loss 6
Total 134 Total 134
Input output
Trifluoroacetic Acid 81 Isopropyl Trifluoroacetate 100
Isopropyl Alcohol 43 Glass Lined Effluent 13
Sulphuric Acid 10 Distillation Residue 14
Total 134 Total 134

Distillation Residue 14 ETP Gypsum 20
Calcium Hydroxide 23 Water (Effluent) 17
Total 37 Total 37
8. Ethyl Trifluoro acetate Route-1 & Route-2
In a glass lined reactor, is charged trifluoro acetic acid and chilled. To this is added Ethanol. On
completion of addition, resin / conc. sulphuric acid is added to the reaction mass. The reaction

mass is refluxed continuously to azeo tropically distill out water. The water is removed from the
reaction mass and the final product is then distilled, collected and packed in drums.
Chemical Reaction:
Reaction Scheme 1:
Reaction Scheme 2:
Material Balance:
Input output
Trifluoroacetic Acid 84 Ethyl Trifluoroacetate 100
Ethanol 34 Effluent 14
Fresh resin 1 Glass Lined Recovered Resin 19
Recovered Resin 19 Reactor Distillation Loss 5
Total 138 Total 138
Input output
Trifluoroacetic Acid 89 Ethyl Trifluoroacetate 100
Ethanol 36 Glass Lined Water Of Reaction 13
Sulphuric Acid 5 Distillation Residue 10
Total 130 Total 130

Distillation Residue 10 Gypsum 15
Calcium Hydroxide 15 ETP Water (Effluent) 10
Total 25 Total 25

9. DL-Mandelic Acid Route-1
To an SS reactor are added benzaldehyde and an aqueous solution of sodium cyanide. To this is
added a solution of sodium bisulphite. The reaction is monitored on HPLC. Once the reaction is
complete, a layer of mandelonitrile separates which is collected. The organic phase is then
washed with toluene. The mandelonitrile and toluene layers are combined and then the toluene
is removed by distillation. Once the distillation is complete, the mandelonitrile is then taken in a
glass lined reactor and aqueous HCl is then added to the same. The reaction mixture is
maintained at room temperature for 12 hours and then to the reaction mass is added toluene.
The aqueous layer is extracted again with toluene and the combined organic extract is then
concentrated to give the final product.
Chemical Reaction:
Route 1:

Route 2:
Material Balance:
Input Output
Benzaldehyde 85 Mandelonitrile 122
Sodium
140 Sodium Sulphite 88
Bisulphite SS Reactor
Sodium Cyanide 64 Effluent 79
Total 289 Total 289

Mandelonitrile 122 Organic Layer 362
HCl Solution 57 Glass HCl Gas to scrubber 10
Fresh DCM 63 Lined
Recovered DCM 192 Effluent 62
Reactor
Total 434 Total 434

Organic Layer 362 Mandelic Acid 100
Glass Recovered DCM 192
Lined Distillation Loss Of DCM 4
Mother Liquor 66
Reactor
Total 362 Total 362

Input Output
Acetophenone 87 Reaction Mass 135
Acetic acid 360 SS Acetic Acid Solution 1083
Chlorine Gas 51 Reactor
Chilled Water 720

Reaction Mass 135 Organic Layer 282
NaOH Flakes 36 Glass Aqueous Layer 371
Water 182 Lined
HCl Solution (28%) 118
Reactor
Dichloromethane 182
Total 653 Total 653

Organic Layer 282 Mandelic Acid 100
Glass Recovered DCM 110
Lined Distillation Loss Of DCM 1
Efffluent 71
Reactor
Total 282 Total 282
10. Trifluoroacetyl L-Lysine (TFAL)
Stage 1: In a clean SS reactor, charge water and caustic flakes. Chill the mixture to 0-5C. Add
L-lysine and chill to -4C. Then slowly TFAE (LIS-5) at 0-5C. Maintain the reaction mass at 0-
5C for 20-25 minutes.
Stage 2: Meanwhile, in another reactor, prepare a brine solution of NaCl in water. Unload half
of this solution.
Stage 3: Now, slowly add the reaction mass from stage 1 to the reactor of stage 2 keeping the
temperature 0-5C. Add HCl to the reaction mass slowly keeping reaction temperature at 0-5C.
Then charge the other 50% brine solution from stage 2. Add some more HCl solution keeping
temp 0-5C. Maintain the reaction for 10-15 minutes. Adjust the pH to 7 in about 3 hours using
HCl solution. Then, prepare another HCl solution with dilution of 1:1 in DM water. With about
1-1.5 liter of this diluted solution, adjust the pH to 6.4 to 6.8 in about 30 minutes, again at 0-5C.
Maintain for 3 hours. Centrifuge the mass. With strong agitation, chill 180 liters D.M water at <
0C (preferably to -5 to -10C) and then was the centrifuge cake 2 times with 90 liters of the pre-

chilled water. Ensure it is a spray wash and not a slurry wash. Spin dry the centrifuge cake for
about 4-5 hours. Vacuum dry the product at 50C till moisture of reaction mass is less than 5%.
Chemical Reaction:
Material Balance:
Input output
DM Water 150 Reaction Mass 294
Catalyst 10
L-Lysine 69
SS Reactor
TFAE 65
Total 294 Total 294

Reaction Mass 294 TFAL 100
NaCl 86 Effluent 468
Water 100
28% HCl Solution 5
SS Reactor
Chilled Water 83
Total 568 Total 568
11. Ethyl-4-phenyl-2-oxobutyrate (LIS-II)
To a glass lined reactor is charged Tetrahydrofuran, Magnesium foil and catalyst. To this is then
added Phenyl Ethyl Chloride slowly. The reaction is then refluxed for 2 hours.
The product from GLR reactor (Grignard Reagent) is then added to the SS reactor in which
Diethyloxalate is already added. On completion of reaction, the reaction mass is quenched with
aq. HCl and washed with DM water. The aqueous layer is sent for THF recovery. Meanwhile,

the organic layer is then subjected to distillation to recovery unreacted diethyl oxalate. The
residue in the reactor is our final product.
Chemical Reaction:
Material Balance:
Input Reactor output

Tetrahydrofuran 100 Grignard Reagent 186
Magnesium Turnings 14 Reflux loss of THF 3
Catalyst 3
GLR Reactor
Phenyl Ethyl Chloride 72
Total 189 Total 189

Grignard Reagent 186 Organic Layer 140
Fresh Diethyl Oxalate 90 Aqueous Layer 566
Recovered Diethyl Oxalate 30
Aq. HCl(10%) 200
SS Reactor
Water 200
Total 706 Total 706

Organic Layer 140 LIS-II 100
Recovered Diethyl Oxalate 30
SS Reactor Distillation Loss 10
Total 140 Total 140

12. Trityl Chloride
To an SS vessel is charged trityl alcohol followed by charging of methanol. The mass is then
cooled to 20-30°C. Sulphuric acid (98%) is then charged in a catalytic quantity. The reaction
mass is stirred at 25-35C for 1-2 hours. The mass is then heated to 45-50C for 3-4 hours. The
reaction is monitored on TLC. The product is then filtered off. The methanol is sent for
recovery and reused in the next reaction.
In another glass lined reactor, charge toluene. The methyl trityl ether from above is then
charged into the reactor followed by activated carbon and sodium bi-sulphite. The reaction is
then stirred for 30 minutes and filtered and washed with toluene. The reaction is then purged
with dry HCl gas at 65-70C and reaction is monitored on TLC. About 75% of the toluene is
distilled off and recovered for the next batch. The remaining product is then chilled to 0-5°C
and stirred for 30 minutes. The product is finally filtered and washed with toluene. The ML is
then reused in the next batch as such.
Chemical Reaction:

Material Balance:
Input output
Trityl Alcohol 150 TME 121
Recovered Methanol 250 SS Reactor Efflent 82
Sulphuric Acid 3
Total 453 Total 453

TME 121 Trityl Chloride 100
Fresh Toluene 23
Recovered Toluene 120 Mother Liquor 232
Mother Liquor 232 GLR Reactor Toluene 120
Dry HCl Gas 50 Aqueous Layer 160
DM Water 100 Dry HCl Gas 34
Total 646 Total 646

NaCl 80 HCl Gas Dry HCl Gas 50
Sulphuric Acid 66 Sodium Sulphate 96
Recovered Sulphric acid 69 Generator Spent Sulphuric Acid 69
Total 215 Total 215

HCl Gas 34 Sodium Chloride 55
40% NaOH Solution 93 Scrubber Water (Effluent) 72
Total 127 Total 127
13. 4-Bromo Phenyl Acetic Acid
To an SS-Reactor is charged 4-Bromobenzyl cyanide. To this is added 50% aqueous NaOH at

40-50°C. The reaction mass is then refluxed for 6-8 hours. On completion, the reaction is
quenched with Aq. HCl solution. The isolated product is filtered and dried and packed.

Chemical Reaction:
Material Balance:

4-Bromobenzyl cyanide 125 4-Bromophenyl Acetic Acid 100
48% Aq. NaOH 120 Effluent 333
Aq. HCl (28%) 188
SS Reactor
Total 433 Total 433
14. 4-Bromo Benzyl Cyanide
To a glass lined reactor, charge chlorobenzene and 4-bromo toluene. To this, add catalyst
AIBN. Raise the temperature of the reaction mass to 85°C. Add Liquid bromine at temperature
range of 85-95°C. On completion, cool to 70°C and wash with 10% sodium carbonate solution
followed by DM water.
In another SS reactor, charge sodium cyanide, DM water and TBAB catalyst. Heat the reaction
mass to 75°C. Slowly add the organic layer from the glass lined reactor into the reaction mass
between 75-85°C. Cool the reaction mass to 70°C and then remove the aqueous layer. Wash
with more DM water. The product is then distilled under reduced pressure to get the final
product.

Chemical Reaction:
Bromine Liquid / Br
60C
Br Br
30% Aq. NaCN /

TBAB
60-70C
CN
Br
Material Balance:

Fresh 4-Bromotoluene 85 Reaction Mass 875
Recovered 4-Bromotoluene 115 HBr 5
Fresh Chlorobenzene 50 Aqueous layer 336
Recovered Chlorobenzene 550
Catalyst A 6
GLR Reactor
Bromine Liquid 110
10% Aq. Na2CO3 150
DM Water 150

Reaction Mass 875 Aqueous Layer 625
DM Water 450 4-Bromotoluene 115
Catalyst B 6 Chlorobenzene - Recovery 550
NaCN 80 4-Bromobenzyl cyanide 100
SS Reactor Residue 21

15. Choline Chloride
To an SS reactor 30% TMA Solution is first reacted with Ethylene Oxide between 80°C to
120°C to form 49% Choline Hydroxide Solution, which in turn is reactedwith 33% HCl to form
Choline Chloride Solution whose ph should be neutral. Water is evaporated from this Solution
and the remaining mass is cooled to lessthan Room Temperature, which in turn is centrifuged to
separate water to formCholine Chloride 98% Crystals.
Chemical Reaction:
N
+ N+
O HO
OH-
HCl
Cl-
N+
HO
Material Balance:

30% Triethylamine Solution 156 Choline Chloride 100
Ethylene Oxide 36 Distilled Water 125
28% HCl 105
SS Reactor Effluent 70
Distillation Loss Of Water 2
Total 297 Total 297

16. 4-Nitro 1H-imidazole (LARM-61)
To a glass lined reactor is charged conc. HNO3 and conc. H2SO4. To this is then charged
imidazole at 0-5C. The reaction is allowed to complete for 4 hours. On completion, to the
reactor is then charged with cracked ice / chilled water. The precipitates are then filtered, dried
and packed.
Chemical Reaction:
Material Balance:

Imidazole 75.00 Final Product 100
H2SO4 124.00 Mother Liquor 345
Oleum (65%) 180.00 GLR Reactor Nox Emission in ppm
Fuming HNO3 66.00
Total 445 Total 445
17. 2-chloro ethyl morpholine HCl (LARM-62)
In a glass lined reactor is charged ethylene dichloride, hydroxyl morph line and thinly chloride
is charged. The reaction is allowed to proceed to completion. On completion, the product
formed is filtered.
The mother liquor is sent for recovery of ethylene dichloride.

Chemical Reaction:
Material Balance:

Hydroxy ethyl morpholine 89.00 2-chloro ethyl morpholine.HCl 100
Thionyl chloride 93.00 Thionyl chloride (SO2gas) 50
Fresh Ethylene dichloride HCl gas 28
Recovered Ethylene dichloride
25.00
420.00
GLR Reactor Ethylene dichloride 420
Vapour loss 21
Solid Residue 8
Total 627 Total 627

SO2 Gas 50 Sodium Sulphite 92
HCl Gas 28 Scrubber Water (Effluent) 141
40%NaOH Solution 155
Total 233 Total 233
18. ACNP (2-Amino-6-chloro-3-nitropyridine)
To a glass lined reactor is charged conc. HNO3 and conc. H2SO4. To this is then charged DCP
(2,6dichloropyridine. The reaction is allowed to complete. On completion, to the reactor is then
charged with cracked ice / chilled water. The precipitates are then filtered as nitro DCP as wet
cake.
To another SS reactor is added IPA. To this is added the nitro DCP wet cake obtained from the
above reaction. To this is then added liquor ammonia solution. The IPA is then distilled off
partially. On about % IPA removal, the product is then obtained which is filtered and dried.
Chemical Reaction:

Cl N Cl conc. HNO3 / Cl N Cl Liq. NH3 Cl N NH2
conc. H2SO4
NO2 NO2
Material Balance:

2,6 -Dichloro pyridine 84.00 Reaction mass 109
Fuming HNO3 72.00 Mother Liquor 597
Con. H2SO4 125.00 GLR Reactor NOX Emission in ppm Limit
DM Water 425.00
Total 706 Total 706

Reaction mass 109.00 Final Product 100
Fresh IPA 32.00 Recovered IPA 500
Recovered IPA 500 GLR Reactor Vapour Loss (IPA) 32
Liq. Ammonia 100.00 Mother Liquor 50
Solid Residue 59
Total 741 Total 741
19. 2-Amino-3-nitro-6-(4-fluorobenzylamino) pyridine (ANFP)
In a SS reactor add 2-amino-3-nitro-6-chloro pyridine and 4-Fluoro benzyl followed by Water

and Sodium Carbonate. Reflux till the reaction is completed. Filter wash and dry the product in
ANFD. Unload the final product. Send ML to ETP.
Chemical Reaction:
F F
Cl
+ N
NO 2
NH2 NH2 HN
M olecular F orm ula: C 5 H 4 C lN 3 O 2
M olecular F orm ula: C 7 H 8 F N
F orm ula W eight: 173.55716 N
F orm ula W eight: 125.1435232
NO 2
NH2
M olecular F orm ula: C 1 2 H 1 1 F N 4 O 2


Material Balance:

ANCP 67.00 ANFP 100
4-Fluoro benzyl amine 51.00 Sodium chloride (by product) 23
Sodium carbonate 41.00 GLR Reactor Water (Liquid waste) 304
DM Water 270.00 Residue (Solid waste) 2
Total 429 Total 429
20. DIKETONE (4,4,4 trifluoro-1-(4-methyl phenyl) butane-1,3-dione)
To an SS reactor is added methanol and sodium methoxide. To this is then added isopropyl
trifluoroacetate and stirred for 30 mins. To this is then added slowly 4-methyl acetophenone and
the reaction mass is refluxed for 6 hours. The methanol is then distilled out with IPA, which is
recovered and used in subsequent reaction. The pH of the rest of the reaction mass is then
adjusted with acetic acid to 6 and reaction mass is cooled and the product filtered. The final
product is then filtered and dried and packed.
Chemical Reaction:

Material Balance:

Fresh Methanol 10.00 Diketone Crude 103
Recovered Methanol 140.00
Sodium Methoxide 25.00 Recovered Methanol 140
Isopropyl Trifluoroacetate 71.00 SS Reactor Sodium Acetate 18
4-methyl Acetophenone 58.00 Distillation Loss 12
Acetic Acid 13.00 Mother Liquor 44
Total 317 Total 317

Diketone Crude 103 Final Product 100
Residue 2
Distillation Loss 1
SS Reactor
Total 103 Total 103

21. 3-CTMPP(3-(2-chloroethyl)-2-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido[1,2-
a]pyrimidin-1-ium chloride)
To a glass lined reactor, is charged 2-aminopyridine, 2-acetylbutyrolactone, dichloromethane

and phosphorous oxychloride. The reaction is allowed to complete. On completion, POCl3 is
recovered using distillation and to the reaction mass is added Aq. NaOH. The pH is adjusted to
7 and the product is filtered and washed with water and used as such for the next process.
The filtered wet cake is then charged in an autoclave along with methanol and Pd / C. The
reaction is completed in 20 hours. On completion, the reaction mass is filtered through celite
bed. To this is added conc. HCl. The product is precipitated. This is then filtered dried and
packed.
Chemical Reaction:
Material Balance:


2-Aminopyridine 74 Reaction mass 133
2-acetylbutyrolactone 101 Effluent 352
Fresh Dichloromethane 6 Recovered DCM 142
Recovred Dichloromethane 142 Recovered POCl3 22
Aq. NaOH (20%)
DM. Water
141
30
GLR Reactor
Fresh Phosphorous
Oxychloride 133
Recovered Phosphorous
Oxychloride 22
Total 649 Total 649

Reaction mass 133 3CTMPP 100
Recovered Methanol 630 Autoclave Pd/C 16
Fresh Pd/C Distillation Residue 96
Recovered Pd/c
1
followed by SS Celite + Carbon 8
16
Charcoal 4 Reactor
Celite 2
Conc. HCl 30.00
Total 850 Total 850
22. Phenylglycine
To an SS reactor is charged a solution of benzaldehyde, ammonium hydrogen carbonate, and

sodium cyanide in methanol and water and is stirred at 65-70° C. for 5 h. concentrate the
solution and transfer to another SS reactor. To this is added 45% NaOH solution, was refluxed
for 4 h at 120° C. The pH of filtrate is to be adjusted by 50% H2SO4 to 7-8. The precipitated
was filtrated and washed with water. The final product is dried under vacuum.
Chemical Reaction:

Material Balance:

Benzaldehyde 74 Aqueous Layer 181
Sodium cyanide 30 Recovered Methanol + Water 388
Ammonium carbonate 15
Methanol 6 SS Reactor
Water 6
Recovered Methanol + Water 388
Caustic Lye 50
Total 569 Total 569

Aqueous Layer 181 Phenylglycine 100
Sulphuric Acid 20 Aqueos ML 101
GLR Reactor
Total 201 Total 201
23. Venlafaxine stage 1 & 2 (1-[2-(dimethylamino)-1-(4-methoxyphenyl)ethyl]cyclohexan-1-ol)
In an SS reactor are added methanol, cyclohexanone, 4-MEP and KOH. The reaction is refluxed
for 72 hours. On completion of reaction, the material is cooled and centrifuged. The methanol
ML is sent for recovery and reuse. The product is dried and may be sold if client requires. It can
be taken further for next stage.
The reaction is continued in SS reactor by charging methanol, raneyni and stage 1. Using
hydrogen gas pressurised reaction is carried out. Once the reaction is complete Methanol is
recovered and the concentrated mass is transferred to another SS reactor for further processing.
IPA/MDC, formaldehyde and formic acid is added to the mass, followed by sparging of HCL
gas for over 12 hrs. When the reaction is complete recover IPA/MDC. The concentration is then
filtered washed and dried in ANFD. The dried product is unloaded.
Chemical Reaction:

CN
O OH OH
CN
KO H / NH2
M ethanol H2 /
+
R aney N ickel
O
M olecular F orm ula: C 6 H 10 O CH3
M olecular Formula: C 9H 9N O O O
Formula W eight: 147.17386
CH3 CH3
M olecular F orm ula: C 15 H 19 NO 2
F orm ula W eight: 245.31686 Molecular Form ula: C 15 H 23 NO 2
Form ula W eight: 249.34862
HCHO / HCOOH
OH CH3
N HCl
CH3
Molecular F orm ula: C 1 7 H 2 8 C lN O 2

O CH3
Material Balance:
In p u t R e a cto r O u tp u t
Com pound Q ty (K G S) Com pound Q ty (K G S)
C y clo h e xa n o n e 60 R e a ctio n M a ss 640
4M EP 70
KOH 10
Fre sh M e th a n o l 20 G LR
R e co v e re d M e th a n o l 480
T o ta l 640 T o ta l 640

R e a ctio n M a ss 640 In te rm e d ia te 1 (v f-1 ) 120
M e th a n o l M L 480
C e n trifu g e E fflu e n t 40

V e n e la fa xin e Sta g e II /
120
In te rm e d ia te 1 V e n e la fa xin e B a se 100
Fre sh M e th a n o l 19 R e co v e re d M e th a n o l 381
R e co v e re d M e th a n o l 381 SSR D istilla tio n lo ss 45
Raney N i 2 H y d ro g e n g a s 3
H y d ro g e n
7

24. 5-Nitroisophthalic Acid Dimethyl Ester (XR-202)
In a glass lined reactor, is charged Toluene, methanol, XR-101 and sulphuric acid. Reflux the
reaction mass for 3 hour. Separate aqueous layer. Transfer the reaction mass to SS reactor.
Charge slowly Sodium bicarbonate solution. On completion of the same, seperate the aqueous
layer and send to ETP. Cool the reaction mass. Filter the reaction mass into an ANFD. Wash
with DM Water. Dry under vacuum and unload the product.
Chemical Reaction:
O O
HO O
H3C
OH O CH3
Methanol
O Conc. Sulphuric Acid O

- + - +
O N O N
O O

Material Balance:
Com pound Q ty (K G S ) Com pound Q ty (K G S )
X R -1 0 1 (5 -n it r o is o R e a c t io n M a s s
p h a t h a lic a c id ) 85 1105
Fre sh M e th a n o l 50 S S R e a cto r
R e co v e re d M e th a n o l 950
S u lp h u r ic 20
T o ta l 1105 T o ta l 1105

R e a c t io n M a s s 1105 X R -2 0 2 100
W a te r 200 M ETHANO L M L 985
AN FD E ffflu e n t 140
D r y in g L o s s o f W a t e r 80
T o ta l 1305 T o ta l 1305

M e th a n o l M L 985 R e co v e re d M e th a n o l 950
D is t illa t io n L o s s O f M e t h a n o l 30
M e th a n o l
D is t illa t io n R e s id u e 5
R e co v e ry
25. 5-Nitroisophthalic Acid Methyl Ester (XR-201)
In a glass lined reactor, is charged Toluene, methanol, XR-101 and sulphuric acid. Reflux the
reaction mass for 3 hour. Separate aqueous layer. Transfer the reaction mass to SS reactor.
Charge slowly Sodium bi-carbonate solution. On completion of the same, separate the aqueous
layer and send toluene layer for recycling. Add carbon to aqueous layer and filter. Take reaction
mass to glass lined reactor and acidify with HCl. Filter the reaction mass into an ANFD. Wash
with DM Water. Dry under vacuum and unload the product.

Chemical Reaction:
O O
HO HO
OH O CH 3
Methanol
O Conc. Sulphuric Acid O

- + - +
O N O N
O O
Material Balance:
XR-101(5-nitro iso
phathalic acid) 175 Aqueous Layer 525
Fresh Toluene 50 SS Toluene Layer 1350
Recovered Toluene 1350 Reacto Dilute Sulphuric Acid 40
Sulphuric Acid 20
Water 50 r
Mother liquor 250
Sodium Bicarbonate 20

Aqueous Layer 525 XR-201 100
conc. HCl 15 Mother Liquor 250
GLR Mother Liquor 190
Total 540 Total 540
26. P-Sulfonyl benzoic acid potassium salt (SB-201)
To an SS reactor is added water, PTSA and KOH. To thisis slowly added KMnO4. This is then
maintained for 24 hours. On completion of reaction, the material is filtered to remove MnO2 as
by-product. The reaction mass is then acidified with HCl in a glass lined rector. The reaction
mass is then filtered in an ANFD and dried under vacuum.

Chemical Reaction:
CH3 COOH
KMnO4
KOH
- +
SO 3H SO 3 K
Material Balance:
In put Reactor Output

P-Sulfonyl
benzoic acid
potassium salt
(SB-101) 95 Aqueous Layer 272
Water 150 MnO2 solid 8
KMnO4 30
SS Reactor
KOH 5
Total 280 Total 280

Aqueous Layer 272 SB-201 100
conc. HCl 15 Effluent 187
GLR
Total 287 Total 287
27. 5-Chlro-2,3-Disulfonamide Aniline (DS-201)
In an SS reactor, is charged water, ammonia, SB-101. Reflux the reaction mass for 3 hour. This
is followed by distillation of ammonia. Transfer the reaction mass to SS reactor. Charge slowly
sulphuric acid solution. On completion of the same, filter the reaction mass into an ANFD.
Wash with DM Water. Dry under vacuum and unload the product.
Chemical Reaction:
Cl Cl
NH3
H2N SO2Cl H2N SO2NH2

SO2Cl SO2NH2
Material Balance:

DS-201 Crude 110 Aqueous Layer 290
Water 50
Mother Liquor 100
Caustic Lye 30
SS Reactor
Total 290 Total 290

Aqueous Layer 290 DS-201 100
Sulphuric Acid 15 Mother Liquor 100
GLR Mother Liquor 105
Total 305 Total 305
28. 3-amino-1,2-propanediol (AP-301)
In a glass lined reactor, is charged water, sulphuric acid, EPC and catalyst. The reaction on
completion is then transferred to a SSR. This is then distilled under reduced pressure to give
water followed by the intermediate. The intermediate is then reacted with ammonia in presence
of water and on completion of the reaction, the ammonia is recovered. This is followed by a
high vacuum distillation of the product.

Chemical Reaction:
Cl
Sulphuric Acid NH3

HO Cl HO NH2
O
Water
HO HO
Material Balance:

EPC 120 IM1 110
Water 150 Distilled Water 160
sulphuric acid 5 SS Residue 6
cesium carbonate 1
Reactor
Total 276 Total 276

IM1 110 Distilled Product 100
Fresh Ammonia 20
Recovered Ammonia 100 Recovered Ammonia 100
Water 50
SSR Distillation Residue 80
Total 280 Total 280
29. N-Methyl-Aminomethyl Naphthalene (NM Base)
To an SSR, is added MMA (monomethyl amine) solution in methanol. To this is added CMN
(chloromethyl naphthalene). The reaction is allowed to complete. On completion, the excess
methanol and MMA are recovered as a solution. The product is then distilled under high
vacuum to give the final product.
Chemical Reaction:

+ H3C NH2
Molecular Formula: CH5N

Formula Weight: 378.93758
Cl NH CH3
Molecular Formula: C11H9Cl Molecular Formula: C12H13N

Formula Weight: 378.93758 Formula Weight: 171.23832
Material Balance:
CMN 120 Reaction Mass 146
MMA 20 Recovered Methanol 250
Methanol 20 Distillation loss 15
Recovered Methanol 250 SS Reactor
Water 1
Total 411 Total 411

Reaction Mass 146 Distilled Product 100
Distillation Residue 41
SSR Distillation loss 5
Total 146 Total 146

CMN 120 Reaction Mass 146
MMA 20 Recovered Methanol 250
Methanol 20 Distillation loss 15
Recovered Methanol 250 SS Reactor
Water 1
Total 411 411

Reaction Mass 146 Distilled Product 100
SSR Distillation loss 5
146 146
30. 1-(3-CHLOROPHENYL)PIPERAZINE (T1)

In a glass lined reactor, is charged Toluene, MCA and Bis-2-chloroethylamine hydrochloride.

Slowly add caustic lye to the reaction mass. On compliance, add toluene to reaction mass.
Remove aqueous later. Distill off the toluene followed by high vacuum distillation of the
product.
Chemical Reaction:
Cl
Cl
NaOH
Cl
+ Cl
NH -NaCl
N
H2N
Molecular Formula: C4H9Cl2N
Molecular Formula: C6H6ClN
Formula Weight: 142.02696 N
Formula Weight: 127.57154 H
Molecular Formula: C10H13ClN2

Material Balance:
FB1 120 R e a c t io n M a s s 620
M SA 200 A Q U EO U S LA YER 750
H E X A M IN E 50
W ATER 500 SSR
F re sh T O LU E N E 50
R e co v e re d T O LU E N E 450
T o ta l 1370 T o ta l 1370

R E A C T IO N M A S S 620 RECO VERED TO LU EN E 450
F re sh D M F 50 A Q U EO U S LA YER 200
R e co v e re d D M F 150 In t e r m e id a t e 200
IB B 50
SSR R e co v e rd D M F 150
K2CO3 30
W ATER 100
T o ta l 1000 T o ta l 1000

M e th a n o l 20 FB2 100
R e co v e re d M e th a n o l 340 A Q U EO U S LA YER 100
RECO VERED
340
T h io n y l C h lo r id e 10 G LR M ETHANO L
H y d r o x y la m in e H C l 50 R E S ID U E 5
In t e r m e d ia t e 200 A Q U EO S LA YER 175
W a te r 100


FB1 120 Reaction M ass 620
M SA 200 AQUEOUS LAYER 750
HEXAM INE 50
W ATER 500 SSR
Fresh TOLUENE 50
Recovered TOLUENE 450

REACTION M ASS 620 RECOVERED TOLUENE 450
Fresh DM F 50 AQUEOUS LAYER 200
Recovered DM F 150 Interm eidate 200
IBB 50
SSR Recoverd DM F 150
K2CO3 30
W ATER 100

M ethanol 20 FB2 100
Recovered M ethanol 340 AQUEOUS LAYER 100
RECOVERED 340
Thionyl Chloride 10
GLR M ETHANOL
Hydroxylam ine HCl 50 RESIDUE 5
Interm ediate 200 AQUEOS LAYER 175
W ater 100
Total 720 Total 720
31. 1-(3-chlorophenyl)-4-(3-chloropropyl) piperazine (T2) hydrochloride
In a stainless reactor add acetone, T1 and NaOH followed by slow addition on CBP. Upon
completion of addition recover all of acetone and transfer mass in another stainless steel reactor
for distillation of product under high vacuum.
Chemical Reaction:

Cl Cl
NaOH /
+ Cl Br Acetone
N N
Molecular Form ula: C 3 H 6 BrCl
N N
H
Cl
Molecular Form ula: C 10 H 13 ClN 2
Form ula W eight: 196.67662 Molecular Form ula: C 12 H 16 Cl 2 N 2
Material Balance:
In p u t R e a cto r
Com pound Q t y (K G S ) Com pound Q t y (K G S )
T1 50 R e a c tio n M a s s 110
A c e to n e 300 D is tille d A c e to n e 330
C a u s tic L y e 30
CBP 60 G LR

R e a c tio n M a s s 110 D is tille d P ro d u c t 100
D is tilla tio n R e s id u e 10
SSR
32. 4-[5-(4-methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonamide
In a SS reactor charge Methanol, 4-MAP, ETA and Sodium methoxide adjust pH with Conc.
HCL and once HCL addition is complete distil out methanol, followed by sellable intermediate.
In an SS reactor add the intermediate, toluene and Sulfonamide hydrazine hydrochloride, reflux
till reaction is complete. Filter, wash and dry the product in ANFD and send ML for Toluene
recovery.

Chemical Reaction:
O CH3
O O
+ F 3C COOEt COOEt
Molecular Formula: C4H5F3O2

H3C
CH3
Molecular Formula: C9H10O Dione (Sellable Intermediate)

Molecular Formula: C13H14O4
NHNH 2HCl
H2NO 2S
H2NO 2S
N N
CF 3
H3C
Molecular Formula: C17H14F3N3O2S

Material Balance:

4MAP 50 CXB Dione 100
ETA 60 Distilled methanol 88
Sodium Methoxide 30 Effluent 22
Methanol 60 SSR
con. HCl 10
Total 210 Total 210

33. Ethyl 2-(4-hydroxyphenyl)-4-methylthiazole-5-carboxylate
Charge DMF, PCP and Sodium Sulphide in stainless steel reactor followed by slow addition on
sulphuric addition. Upon completion of addition filter via CF and transfer ML to glass lined
reactor and the wet cake sent to ETP. In glass lined reactors add E2CAA slowly, after addition
distill out DMF and then add water and methanol. Filter and dry the product sending ML for
recovery.
Chemical Reaction:
CN Sulphuric
CSNH 2 O O
Acid
+ Na 2S + H 3C CH3
HO DMF O
HO
Cl
Molecular Formula: C7H5NO Molecular Formula: C 7H7NOS
Molecular Formula: C 6H9ClO 3
Formula Weight: 119.1207 Formula W eight: 153.20158
Formula W eight: 164.58686
Methanol
CH3
N O
H 3C
HO
Molecular Formula: C13H13NO 2S

Material Balance:
Com pound Qty (KGS) Com pound Qty (KGS)
Fresh DM F 30 Reaction M ass 330
Recovered DM F 220
PCP 50 SODIUM SULPHATE 60
SODIUM SULPHIDE 60
SULPHURIC ACID 30
SSR
390 390

Reaction M ass 330 FB1 100
W ATER 10 RECOVERED DM F 220
RECOVERED
E2CAA
50
GLR M ETHANOL
180
Fresh M ETHANOL 20 RESIDUE 5
Recovred M ethanol 180 AQUEOS LAYER 85
590 590

34. Ethyl-2-(3-Cyano-4-isobutoxyphenyl)-4-methyl-1,3-thiazole-5-carboxylate(FBT)
Charge MSA, FB1, Hexamine and Toluene in a glass lined reactor and reflux till reaction
complies. Add process water once on compliance, separate the aqueous layer and treat in ETP.
Transfer the organic layer to a stainless steel reactor and add DMF, IBB and K2CO3, maintain
till reaction complies. On compliance distill out all the Toluene. Once toluene is distilled add
process water, filter and Dry in ANFD to use in next step. Add FB2 in glass lined reactor
followed by addition of TC once reaction is completed filter and dry product to sell.
Chemical Reaction:
CH3
CH3
N O
N O
OHC
Hexamine S
S
Methanesulphonic H3C
H3C
HO
HO acid
Molecular Formula: C14H13NO3S
Molecular Formula: C13H13NO2S Formula Weight: 275.32292
IBB / K2CO3
DMF
CH3
CH3
N O
N O
OHC
NC S
S H2SO4
H3C
H3C H3C
H3C O
O
H3C
H3C
Molecular Formula: C17H19NO3S
Molecular Formula: C17H18N2O2S

Material Balance:

FB1 120 Reaction Mass 620
MSA 200 AQUEOUS LAYER 750
HEXAMINE 50
WATER 500 SSR
Fresh TOLUENE 50
Recovered TOLUENE 450

REACTION MASS 620 RECOVERED TOLUENE 450
Fresh DMF 50 AQUEOUS LAYER 200
Recovered DMF 150 Intermeidate 200
IBB 50
SSR Recoverd DMF 150
K2CO3 30
WATER 100

Methanol 20 FB2 100
Recovered Methanol 340 AQUEOUS LAYER 100
RECOVERED
340
Thionyl Chloride 10 GLR METHANOL
Hydroxylamine HCl 50 RESIDUE 5

Intermediate 200 AQUEOS LAYER 175
Water 100
Total 720 Total 720
35. Exo,exo-2,3-camphanediol(CDO)
Charge Camphorquinone, Lithium aluminium hydride & dry ether in SS reactor. Once the
reaction is complete give it a Sulphuric acid treatment followed by a washing with Sodium
hydroxide solution in water. Finally add magnesium sulfate to dehydrate and transfer the crude
to another SS reactor. Initially distill out dry ether and water followed by product under high
vacuum.

Chemical Reaction:
Material Balance:
Camphorquinone 103 Reaction Mass 303
Ether 10 AQUEOUS LAYER 130
Recovered Eher 190
Lithium Aluminium Hydride 30
Dilute HCl (10%) 100
SSR
Total 433 Total 433

REACTION MASS 303 Finished Product 100
Distilled Ether 190
SSR Distillation Residue 4
Distillation Loss 9
Total 303 Total 303
36. 3-Ethyl-4-methyl-pyrolidine-2-one
In a SS reactor charge Ethyl acetate, ethyl bromide, sodium methoxide and methanol. Reflux
for over 12 hours, recover methanol and transfer to another SS reactor. Add water, sodium
cyanide, sodium bisulfite and sulphuric acid stir and separate aqueous layer and send to ETP.
Transfer the organic layer to Autoclave. Add methanol and raneyni and carry out the reaction
under Hydrogen pressure. Once the reaction is completed recover methanol and transfer
reaction mass to a glass lined reactor. Add theonyl chloride to the reaction mass and scrub SO2
and HCL. Once the addition is complete transfer to SS reactor and charge Ethylacetate, water
and soda ash. Separate the aqueous layer and send it to ETP and recover over half of ethyl
acetate. Filter after chilling in ANFD wash, dry and unload the final product. ML should be
recycled.

Chemical Reaction:
O
O
O O
Sodium Methoxide O O
H3C
H3C + H3C
CH3 Br Methanol CH3
Molecular Formula: C6H10O3 CH3

Formula Weight: 130.1418 Molecular Formula: C8H14O3
Sodium Cyanide
NaHSO3
H3C
O O
H i)H2 / Raney Ni O OH
O N O N
Soda Ash H3C CN
ii) Thionyl CH3
Chloride
CH3 CH3 CH3
CH3 CH3
Molecular Formula: C9H13NO2 Molecular Formula: C9H15NO3
Molecular Formula: C7H11NO Formula Weight: 167.20502 Formula Weight: 185.2203

Material Balance:

Ethyl Acetoacetate 103 Reaction Mass 240
Fresh Methanol 50
Recovered Methanol 150 Recovered Methanol 150
Ethyl Bromide 60
SSR Sodium Bromide 73
Sodium Methoxide 100
Total 463 Total 463

REACTION MASS 240 Reaction mass 217
Aqueous Layer 278
Water 150
sodium bisulfite 50 SSR
sodium cyanide 30
sulphuric acid 25
Total 495 Total 495

Reaction mass 217 Reaction mass 242
Raney Nickel 10 Autoclave Hydrogen Gas 10
Hydrogen Gas 25
Total 252 Total 252

Reaction mass 242 Reaction mass 237
Thionyl Chloride 15 GLR SO2 + HCl Gas 20
Total 257 Total 257

Reaction mass 237 Finished Product 100
Aqueos Layer 257
Water 100
Fresh Ethyl Acetate 50
SSR Recovered Ethyl
Recovered Ethyl Acetate 100
100 Acetate
Soda Ash 30 Distillation Residue 60
Total 517 Total 517

37. Adrenaline (ADIF)
In a SS reactor charge LIAL H4, Adrenalone and THF. Reflux till reaction is complete followed
by the distillation of THF. Transfer crude to another SS reactor addsulphuricacide, water and
toluene. Separate aqueous layer and send to ETP. Chill the mass and filter, wash and dry the
product and in ANFD. Unload the product. Send ML for toluene recovery.
Chemical Reaction:
O
OH
HO
LiAlH4
HO
NH
NH
HO CH3
HO CH3
Molecular Formula: C9H11NO3

Molecular Formula: C9H13NO3
Material Balance:

Adrenalone 112 Reaction Mass 177
Fresh THF 25
Recovered THF 275 Recovered THF 275
Lithium Aluminium Hydride 40 SSR
Total 452 Total 452

Reaction Mass 177 Adrenaline 100
Aqueous Layer 211
Water 100
Sulphuric Acid 30 SSR Recovered 140
Toluene 10 Toluene
Resiude 2
Recovered Toluene 140 Distilation loss 4
Total 457 Total 457

38. Trans-4-aminocyclohexanol
To an SS autoclave, charge paracetamol, rhodium and water. Increase pressure to 10kg with
hydrogen. On completion of reaction, cool to RT. Release the pressure. filter the reaction mass
and recycle rhodium. Take the filtrate; distill off water under reduced pressure. Add methanol
and caustic lye and maintain at 45C for 32 hours. On completion of reaction, adjust the pH to 3
with conc. HCl, and filter and dry the product.
Chemical Reaction:
OH OH
OH
Hydrogen (G)
NaOH
Rhodium
Methanol
Water
NH NH2 HCl
CH 3CO HN
COCH 3
MaterialBalance:
Input Reactor
Paracetamol 100 Reaction Mass 425
Water 10 Hydrogen gas 10
Recovered water 290 Rhodium sludge 5
Fresh Rhodium 5
Recovered Rhodium 5
Autoclave
Hydrogen 30
Total 440 Total 440

Reaction Mass 425 Trans-4-aminocyclohexanol
100HCl
Caustic Lye 30 Recovered Water 290
Recovered Methanol 140
Fresh Methanol 10 SSR
Recovered Methanol 140 Distillation loss 5
HCl (g) 10 Mother liquor 80
Total 615 Total 615

39. Isoproternol (ISL)
In a SS reactor charge Isopropyl amine, chloroacetyl catechol and water. Reflux this reaction is
completed. Transfer in another SS reactor and give washes of Toluene and water. Separate
aqueous layer and send to ETP. Chill the organic layer and filter, wash and dry the product in
ANFD. Unload the product. Send ML for Toluene recovery.
Chemical Reaction:
Cl O
HO HO
NH
HO H3C
NH2 HO CH3
H3C
H3C
Material Balance:
Reactor Output
Chloroacetyl Catechol 112 Reaction Mass 312
Water 150
Isopropyl amine 50
Autoclave
Total 312 Total 312

Reaction Mass 312 Isoproternol (ISL) 100
Fresh Toluene 3
Aqueous ML 265
Recovered Toluene 97 SSR
HCl 60 Recovered Toluene 97
Distillation loss 5
Total 472 Total 472

40. QuetiapineFumarate
Dibenzo is converted to its imino chloride (QT-I) using phosphorous oxychloride, which is
further condensed with 1-[2-(2-hydroxyethoxy) ethyl] piperazine (HEEP) in the presence of
sodium carbonate to obtain Quetiapine base. The Quetiapine base is then converted to its
fumarate salt using fumaric acid in ethanol. Ethanol denatured with toluene has been used in the
process.
Chemical Reaction:

Material Balance:

Dibenzo 60 Im inochloride (QT1) 79
phosphorous oxychloride 50 Recovered Triethyl Am ine 9
Fresh Triethyl Am ine 1
Triethyl Am ine 9 Aqueous NaCl 62
Caustic Lye 30
SSR
Total 150 Total 150

Im inochloride (QT1) 79 Quetiapine Furm arate 100
Recovered M ethanol 188

HEEP 37
Distillation Loss 12
Soda Ash 30 SSR
Furm aric Acid 16 Distillation Residue 15
Fresh M ethanol Sodium Chloride 21

12
Recovered M ethanol 188 Carbon Dioxide 18
Hydrogen Gas 8
Total 362 Total 362
41. Minodronic Acid
2‐Aminopyridine is reacted with Chloroacetaldehyde in the presence of sodium bicarbonate in

dichloromethane gives Imidazo [1, 2‐a] pyridine (stage‐I).Stage‐I is reacted with ethyl oxalyl
chloride in toluene yields Imidazo[1,2‐a]pyridine‐3‐yl‐acetic acid ethyl ester, which is further
hydrolyzed with potassium hydroxide to give Imidazo[1,2‐a]pyridine‐3‐yl (oxo) acetic acid
which is reacted with hydrazine hydrate in the presence of potassium hydroxide in water to give
stage‐II. Stage‐II is reacted with phosphorous acid and phosphorous trichloride. The resultant
product is hydrolyzed with aqueous HCl solution to give 1‐Hydroxy‐2‐(Imidazo [1, 2‐a]
pyridine‐3‐yl) ethane‐1, 1‐bis (phosphonic acid) monohydrate (Crude Minodronic acid). This is
purified with dilHCl solution which gives pure Minodronic acid.

Chemical Reaction:
Material Balance:
S T A G E -I
In p u t R e a cto r o u tp u t
2 A m in o P y r id in e 53 A q u e o u s E f f lu e n t 228
C h lo r o A c e t a ld e h y d e 98 C a r b o n D io x id e 27
S o d iu m B ic a r b o n a t e S o l. 150 S S R e a cto r S ta g e 1 -O u tp u t 46
T o ta l 301 T o ta a l 301
S T A G E -II-A
S ta g e 1 46 A q u e o u s E f f lu e n t 103
E t h y l O x a ly l C h lo r id e 148 C a r b o n D io x id e 2
S S R e a cto r S ta g e 2 A -O u tp u t 89
S T A G E -II-B
S ta g e 2 A 89 A q u e o u s E f f lu e n t 15
W a te r 8
S S R e a cto r S ta g e 2 B -O u tp u t 82

STA G E-II-C
S ta g e 2 B 82 N itro g e n g a s 30
S ta g e 2 C -
P o ta s s iu m H yd ro x id e 25 77
O u tp u t
SS R eacto r
T o tal 107 T o tal 107

STA G E-II

E va p o ra tio n
S ta g e 2 C 77 3
SS R eacto r lo s s
H yd ro c h lo ric A c id 16 S ta g e 2 -O u tp u t 90
STA G E-III

E va p o ra tio n
S ta g e 2 90 1
lo s s
H yd ro c h lo ric A c id 110 SS R eacto r S ta g e 3 -O u tp u t 107
Aqueous
PC L3 276 430
E fflu e n t
W ate r 62
STA G E-IV

Aqueous
S ta g e 3 107 6
E fflu e n t
SS R eacto r E va p o ra tio n
lo s s
1
S ta g e 4 -O u tp u t 100
T o tal 107 To tal 107
42. NISOLDIPINE
2‐nitro benzaldeyde is condensed with Isobutyl acetoacetate in presence of Formic acid and
Piperidine at 40‐45°C to give Monoisobutyl ester. Monoisobutyl ester is reacted with 3‐amino
crotonic acid methyl ester in presence of 4‐Dimethyl amino pyridine at 80‐85°C to give
Nisoldipine Crude. Nisoldipine Crude is purified in the mixture of Acetone: Water to give
Nisoldipine.
Chemical Reaction:

Material Balance:

2-Nitrobenzaldehyde 63
SS Reactor Aqueous Effluent 5
Isobutyl Acetoacetate 62 Stage1-Output 120
Total 125 Total 125
STAGE-II
2-Nitrobenzylidine
Aceto acetic acid 120 Aqueous Effluent 91
Isobutyl Ester
Methyl-3-Am ino
71 Evaporation Loss 1
Crotonate
SS Reactor
Stage 2-Output 100
Total 192 Total 192
43. METAXALON
Stage‐I: Preparation of 2‐[(3,5‐Dimethylphenoxy)methyl]oxirane

A mixture of 3, 5‐Dimethylphenol and Epichlorohydrine is stirred with aqueous Potasssium
hydroxide at 40oC. Water is distilled out under vacuum after the reaciton. The liquid crude
product 2‐ [(3, 5‐Dimethylphenoxy) methyl]oxirane obtained is taken as such for the next
reaction.
Stage‐II: Preparation of 5‐[(3,5‐dimethylphenoxy)methyl]‐1,3‐oxazolidin‐2‐one
(Metaxalone)
To a solution of 2‐[(3,5‐Dimethylphenoxy)methyl]oxirane in N,N‐Dimethylformamide, is
added Ethylcarbamate and catalytic amount of Triethylamine. The reaction mixture is heated at
120-125oC till the completion of the reaction. After the reaction, isolated solid is filtered once,
which is purified by stirring with isopropyl alcohol to get
5‐[(3,5‐dimethylphenoxy)methyl]‐1,3-oxazolidin‐2‐one (Metaxalone).

Chemical Reaction:

Material Balance:
STAGE-I
3,5-Dim ethylphenol 184 Aqueous Effluent 263
Epichlorohydrine 139 Evaporation Loss 3

Aq. Potassium SS Reactor
104 Stage1-Output 161
Hydroxide
Total 427 Total 427

STAGE-II
Stage 1 161 Aqueous Effluent 158
Ethyl Carbam ate 85 Evaporation Loss 6
Triethyl Am ine 18 SS Reactor Stage 2-Output 100
Total 264 Total 264
44. AGOMELATINE
Catalytic hydrogenation of (7‐Methoxy‐1‐naphthyl) acetonitrile using Methanol and Ammonia
gives 2‐(7‐Methoxy‐1‐naphthyl) ethanamine. Condensation of 2‐(7‐Methoxy‐1‐naphthyl)
ethanamine with acetyl chloride in presence of base gives crude Agolelatine. Which on
purification gives final Agomelatine API.
Chemical Reaction:


Material Balance:
STAGE-I
Reactor Output
2-(7-methoxy-1-
123 Isopropyl Alcohol Recovery 69
napthyl)Acetonitrile
Hydrogen Gas 2 Isopropyl Alcohol Recovery Loss 12
Fresh Isopropyl Alcoho HCl 22 SS Reactor Evaporation loss 2
Recoverey Isopropyl Alcoho

69 Stage1-Output 133
HCl
Total 216 Total 216
STAGE-II
Stage1-Output 133
2-(7-methoxy-1-
napthyl)ethylamine 123 Recovered Acetic acid 52
hydrochloride
Anhydrous Sodium Acetate 52 Sodium Chloride 76
SS Reactor
FreshAnhydrous Acetic 11 Stage 2-Output 100
Recovered Acetic acid 52 Effluent 143
Total 371 Total 371
45. ILOPERIDONE
Reaction of 1‐(4‐hydroxy‐3‐methoxyphenyl) ethanone with 1‐bromo‐3‐chloropropane in

presence of potassium carbonate gives 1‐[4‐(3‐chloropropoxy)‐3‐methoxyphenyl] ethanone.
Condensation of 1 ‐ [4 ‐ (3‐chloropropoxy)‐3‐methoxyphenyl]ethanone with
6‐fluoro‐3(4¬piperidinyl)‐1,2‐benzisoxazole hydrochloride in presence of potassium carbonate
gives crude Iloperidone. Iloperidone crude is the treated with Tartaric acid to produce Tartarate
salt of Iloperidone, which on basification with ammonia to furnish pure Iloperidone.
Chemical Reaction:

Material Balance:
STAGE-I

4 M ethoxy-3-hydroxy
55 Aqueous Effluent 121
Acetophenone
1-Brom o-3-
104 Evaporation Loss 6
Choloropropane
Potassium Carbonate 46
SS Reactor Carbon Dioxide 7
Stage1-Output 71
Total 205.00 Total 205.000
STAGE-II
Stage-1 71 Aqueous Effluent 124
6-Fluoro-3-(4-piperidinyl)-
1,2-benzisoxazole 76 Evaporation Loss 4
hydrochloride
SS Reactor
Potassium Carbonate 51 Stage 2-O utput 100
Sodium Brom ide 30
Total 228 Total 228

STAGE-III
Iloperidone M ethanol 100.000
Stage 3-O utput 100

SS Reactor
Total 100 Total 100

46. FEBUXOSTATE (2-(3-Cyano-4-isobutoxyphenyl)-4-methyl-1,3-thiazole-5-carboxylic

acid)
Charge Methanol and FBT in stain less reactor followed by slow addition of NaOH on
completion add charcoal and then recover methanol. Then remove carbon to send to ETP. Filter
the mass in ANFD, wash and dry the final product.
Chemical Reaction:
CH3 CH3
N N O
O NaOH
NC NC
S S
Methanol OH
H3C H3C
H3C
O O
H3C H3C
Molecular Formula: C17H18N2O2S Molecular Formula: C15H14N2O3S

Material Balance:
E th y l 2 -(4 -
h y d r o x y p h e n y l) - 4 -
110 E f f lu e n t 200
m e t h y lt h ia z o le - 5 -
c a r b o x y la t e
F re s h M e th a n o l 44 R e c o v e re d M e th a n o l 256
R e c o v e re d M e ta h a n o l 256 D is t illa t io n L o s s 35
S S R e a cto r
C a u s t ic F la k e s 184 F e b u x o s ta t C ru d e 103
T o ta l 5 9 4 .0 0 0 T o ta l 5 9 4 .0 0 0
S T A G E -II

F e b u x o s ta t C ru d e 1 0 3 .0 0 0 F e b u x o s t a t F in a l 100
F r e s h T o lu e n e 2 8 .0 0 0 R e c o v e r e d T o lu e n e 1172
R e c o v e r e d T o lu e n e 1 1 7 2 .0 0 0 S S R e a cto r D is t illa t io n R e s id u e 5
C a rb o n 2 .0 0 0 D is t illa t io n L o s s 23
C a rb o n 5
T o ta l
T o ta l 1305 1305

47. WARFARIN sodium
2‐Hydroxy acetophenone is condensed with diethyl carbonate in presence of sodium methoxide

in toluene to give 4‐Hydroxy Coumarin. 4‐Hydroxy Coumarin is reacted with benzal acetone in
presence of Triethyl amine in water to give Warfarin acid. Warfarin sodium is formed by
reaction with sodium hydroxide in a mix of methanol and isopropyl alcohol at 20‐25°C.
Chemical Reaction:

Material Balance:
2 -H yd ro x y
77 A q u e o u s E f f lu e n t 173
A c e to p h e n o n e
D ie t h y l C a r b o n a t e 100 E v a p o r a t io n lo s s 3
S S R e a cto r 4 -H yd ro x y
S o d iu m M e t h o x id e 76 77
C o u m a r in e
S T A G E -II

4 - H y d r o x y C o u m a r in e 77 E f f lu e n t 51
B e n z a l A c e to n e 69 S ta g e 2 -O u tp u t 100
T r ie t h y la m in e 5 S S R e a cto r

48. MEXILETINE HYDROCHLORIDE
Stage‐I: Preparation of 1‐(2’, 6’‐dimethylphenoxy)‐2‐propane oxime
2, 6‐xylenol is reacted with mono‐Chloro acetone in presence of potassium carbonate and

potassium iodide in acetone to gives in‐situ intermediate. This is reacted with hydroxyl amine
HCl in the presence of sodium carbonate in to toluene gives Stage‐I.
Stage‐II: Preparation of 1‐(2’,6’‐dimethylphenoxy)‐2‐propane amine (Mexiletine base)
Catalytic Hydrogenation of oxime derivative in methanol using Raney Ni gives Mexiletine

Base.
Stage‐III: Preparation of 1‐(2’, 6’‐dimethylphenoxy)‐2‐propane amine hydrochloride
Mexiletine Hydrochloride prepared from Mexiletine Base by adding Methanolic HCl in

Acetone
Chemical Reaction:


Material Balance:

2-phenyl ethanol 78 Aqueous Effluent 139
Epichlorohydrine 64
SS Reactor Evaporation Loss 2
Potasium Carbonate 106 Carbon Dioxide 9
Potassium Iodide 6 Stage 1A-Output 104
Total 254 Total 254
STAGE-I
p-Methoxy-Benzyl
104 Aqueous Effluent 167
acetone (Stage 1A)
Hydroxylamine
Hydrochloride
65
Sodium Carbonate 141 Stage 1-Output 137
Total 310 Total 310

STAGE-II
Stage 1 137 Aqueous Effluent 39
Hydrogen Gas 3 SS Reactor Evaporation Loss 1
0 Stage 2-Output 100
Total 140 Total 140

STAGE-III
Mexiletine(Stage 2) 100 Aqueous Effluent 121
Hydrogen Gas 22 SS Reactor Evaporation Loss 1
Water 100 Stage 3-Output 100
Total 222 Total 222
49. FELODIPINE
2, 3‐dichloro Benzaldehyde is condensed with Methylacetoacetate in presence of Formic acid

and Piperidine at 60‐65°C to give Monomethyl ester. Monomethyl ester is reacted with 3‐amino
crotonic acid ethyl ester at 80‐85°C to give Felodipine Crude. Felodipine Crude is purified in
the mixture of Cyclohexane: Isopropyl alcohol to give Felodipine.

Chemical Reaction:
Material Balance:
ST A G E -I
2 ,3 D ic h lo ro
67 A q u e o u s E fflu e n t 13
B e n za ld e h yd e
M e th yl A c e to A c e ta te 47 E va p o ra tio n lo s s 1
SS R e a cto r

ST A G E -II
S ta g e 1 -O u tp u t 100 A q u e o u s E fflu e n t 56
3 -A m in o C o to n ic a c id
63
SS R e a cto r E va p o ra tio n lo s s 7
E th yl e s te r

50. CLOPIDOGREL BISULFATE
The reaction of 2‐chlorophenylglycine with Thionyl chloride & methanol at RT for 48 hrs gives
Hydrochloride salt of Methyl‐α‐amino(2‐chlorophenyl)acetate(Stage‐I) which is then react with
sodium bicarbonate & Ethyl acetate followed by Methanol & L‐(+)‐tartaric acid gives
L‐(+)¬Tartrate salt of S‐Methyl‐α‐amino(2‐chlorophenyl) acetate(Stage‐II) Then Tartrate salt
(stage‐II) reacts with sodium bicarbonate & dichloromethane followed by Tosylate of
2‐Thiophene ethanol(stage‐III) & K2HPO4 gives Methyl
(2S)‐(2‐chlorophenyl){[2‐(2‐thienyl)ethyl] amino}acetate(stage‐IV). Stage‐IV reacts with (41%)
formaldehyde solution followed by Conc. Sulphuric acid to gives Clopidogrelbisulfate
(stage‐V).
Chemical Reaction:

Material Balance:
STA G E-I
Input Reactor O utput
Com pound Q ty (KG S) Com pound Q ty (KG S)
D L-2-cholorophenyl R ecovered
214 1104
glycine M ethanol
T hionyl C hloride 100 SS Reactor S ulphur D ioxide 68
M ethanol 126 S tage 1-O utput 310
R ecovered M ethanol 1104 H Cl G as 33
D istillation Loss 29
STA G E-II
S tage-I 310 A queous E ffluent 479
S odium B icarbonate
336 C arbon D ioxide 57
S olution
SS Reactor
T artaric A cid 90 S tage 2-O utput 350
W ater 150
Total 886 Total 886

STA G E-III
S tage 2-O utput 350 E ffluent 305
T riethyl am ine 198 SS Reactor E vaporation Loss 16
p- toluene S ulphonyl
78 S tage 3-O utput 305
chloride
626 626
STA G E-IV -A
S tage-III 305 E ffluent 284
S odium B icarbonate 183 SS Reactor C arbon D ioxide 39
S tage 4A -O utput 165
Total 488 Total 488
STA G E-IV

S tage 4A -O utput 165 A queous E ffluent 1224
D ipotassium hydrogen
151 S tage 4-O utput 140
sulphate
2-T hienylethyl para-
159 SS Reactor
toluene sulphonate
H ydrochloric Acid 65
D M w ater 824
1364 1364

STAGE-V
Stage-IV 140
Aq.Formaldehyde 135 Stage 5-Output 128
Total 275 Total 275
STAGE-VI
Free Base 128 Aqueous Effluent 263
Sulphuric Acid 37
Water 200 Stage 6-Output 100
Total 365 Total 365
51. RABEPZOLE SODIUM
Stage‐I: 2‐[{4‐(3‐Methoxy propoxy)‐3‐methyl pyridine‐2‐yl} methyl thio] 1H benzimidazole
2‐Hydroxymethyl‐4‐(3‐methoxypropoxy)‐3‐methyl pyridine hydrochloride (RAB/Hydroxy)

(KSM I) is reacted with thionyl chloride in MDC to get
2‐Chloromethyl‐4‐(3‐methoxypropoxy)‐3‐methyl pyridine hydrochloride (RAB/Chloro) is
reacted with 2‐mercapto benzimidazole in presence of sodium hydroxide in methanol to form
rabeprazole sulphide (RAB/I).
Stage‐II: 2‐[{4‐(3‐Methoxy propoxy)‐3‐methyl pyridine‐2‐yl} methyl sulfinyl ] 1H

benzimidazole (RAB/II) from 2‐[{4‐(3‐Methoxy propoxy)‐3‐methyl pyridine‐2‐yl} methyl thio]
1H benzimidazole
Rabeprazole sulphide is reacted with sodium hypochlorite in mixture of isopropyl alcohol and
methanol to form rabeprazolesulphoxide (RAB/II).
Stage‐III: Rabeprazole sodium
Rabeprazolesulphoxide is reacted with sodium hydroxide in methanol to form rabeprazole

sodium.

Chemical Reaction:

Material Balance:
STAGE-I
RAB/Hydroxy 110 Aqueous Effluent 34
Thionyl Chloride 64 Evaporation Loss 2
SS Reactor Sulphur Dioxide 28
Stage 1-Output 110
Total 174 Total 174
STAGE-II

Stage 1-Output 110 Aqueous Effluent 90
2-Mercepto Benzimidazole 65 Evaporation Loss 20

SS Reactor
Sodium Hydroxide 49 Stage 2-Output 114
Total 224 Total 224

STAGE-III
Sodium Hypochloride 405 SS Reactor Evaporation Loss 3
Stage 3-Output 105
Total 519 Total 519
STAGE-IV
Sodium Hydroxide 81 SS Reactor Evaporation Loss 5
Stage 4-Output 100
Total 186 Total 186
52. Celecoxib (CXB) 4-[5-(4-methylphenyl)-3-(trifluoromethyl)pyrazol-1-

yl]benzenesulfonamide
In a SS reactor charge Methanol, 4-MAP, ETA and Sodium methoxide adjust pH with Conc.
HCL and once HCL addition is complete distil out methanol, followed by sellable intermediate.
In an SS reactor add the intermediate, toluene and Sulfonamide hydrazine hydrochloride, reflux

till reaction is complete. Filter, wash and dry the product in ANFD and send ML for Toluene
recovery.
Chemical Reaction:
O CH3
O O
+ F 3C COOEt COOEt
Molecular Formula: C4H5F3O2

H3C
CH3 Formula Weight: 142.0765096
Molecular Formula: C9H10O Dione (Sellable Intermediate)

Molecular Formula: C13H14O4
NHNH 2HCl
H2NO 2S
H2NO 2S
N N
CF 3
H3C
Molecular Formula: C17H14F3N3O2S


Material Balance:

4-[5-(4-methylphenyl)-3-
CXB Dione 122 (trifluoromethyl)pyrazol-1- 100
yl]benzenesulfonamide [
Fresh Toluene 30 Distilled Toluene 370
Recovered Toluene 370 SSR
Sulfonamide 44 Distillation Loss 96
Water 10 Aqueous Mother Liqor 10
Total 576 Total 576
53. DERIFENACIN
Stage‐I: Preparation of 3(S)‐(+)‐(1‐Carbamoyl‐1,1‐diphenylmethyl) pyrrolidine

L‐(+)‐tartrate :
3‐(S)‐(+)‐(1‐Cyano‐1,1‐diphenylmethyl) pyrrolidinehydrobromide (KSM I) is hydrolysed using

diluted Sulfuric acid which on basification with sodium hydroxide and further extraction with
MDC provides 3(S)‐(+)‐(1‐Carbamoyl‐1,1‐diphenylmethyl) pyrrolidine.
3(S)‐(+)‐(1‐Carbamoyl‐1, 1¬diphenylmethyl) pyrrolidine L‐(+)‐tartrate was isolated as L (+)
tartaric acid salt in absolute alcohol.
Stage‐II: Preparation of Darifenacin hydro bromide:
3(S)‐(+)‐(1‐Carbamoyl‐1,1‐diphenylmethyl) pyrrolidine L‐(+)‐tartrate reacts with

5‐(2¬Bromoethyl)‐2,3‐dihydro‐1‐benzofuran in the presence of potassium carbonate in DMF to
give Darifenacin base which on treatment with aqueous HBr and Acetone to give
DarifenacinHydrobromide. It is then purified in absolute alcohol.

Chemical Reaction:

Material Balance:
S T A G E -I
R e a cto r O u tp u t
KSM I 230 A q u e o u s E f f lu e n t 81
S o d iu m H y d r o x id e 30 S S R e a cto r E v a p o r a t io n lo s s 4
S T A G E -II
S ta g e ‐I 175 A q u e o u s E f f lu e n t 173
S o d iu m H y d r o x id e 26 E v a p o r a t io n lo s s 8
S u lp h u r ic A c id 46 S S R e a cto r S ta g e 2 -O u tp u t 143
T a r t a r ic A c id 77
S T A G E -III
S ta g e ‐II 143 A q u e o u s E f f lu e n t 240
K S M II 76 E v a p o r a t io n lo s s 137
P o t a s s iu m C a r b o n a t e 228
S S R e a cto r S ta g e 3 -O u tp u t 100
H y d r o g e n B r o m id e 30
54. ETORICOXIB
Stage‐1 Ketosulfone is reacted with CPT‐Phosphate in presence of Potassium tert‐Butoxide in

Tetra hydrofurane to give Etoricoxib crude.
Stage‐2 Etoricoxib crude recrystallized from IPA‐Hexane to give Etoricoxib
Chemical Reaction:


Material Balance:
STA G E-I

A cetic A cid 220 A cetone R ecovery 265
F resh A cetone 5 A cetone R ecovery Loss 5
R ecovered A cetone 265 IPA Recovery 929
A m m onia S olutionb 1100 IPA Recovery Loss 38
CPT-Phosphate 252 M ethanol Recovery 926
D M w ater 4530 M ethanol Recovery Loss 40
H ydroxylam ine H ydrochloride 12 Toluene Recovery 2120
H yflo 12 Toluene Recovery Loss 200
Fresh IPA 41 Aqueous Effluent 6580
Recovered IPA 929 Stage 1-O utput 111
Ketosulfone 150
Fresh M ethanol 41 SS Reactor
Recovered M ethanol 926
Potassium Tetrabutoxide 66
Sodium Acetate 30
Sodium H ydroxide 315
Fresh Toluene 200
Recovered Toluene 2120

STA G E-II
A ctivated C harcoal 2 IP A R ecovery 1447
S tage 1 111 IP A R ecovery Loss 81
Spent Carbon 9
H exane
H yflo
26
5
Fresh IPA 82 Stage 2-O utput 100
Recovered IPA 1447

55. Memantine HCl

1‐bromo‐3,5dimethyladmantane is react with Acetonitrile and sulfuric acid gives 1‐acetamido-
3,5dimethyl admantane which upon reaction with sodium hydroxidein presence of PEG‐400
gives Memantinebase . BY addition of Conc HCl in memantine base gives memantine
Hydrochloride crude and which upon purification gives Memantine HCL
Chemical Reaction:

Material Balance:
STAGE-I

1-Bromo-3,5-Dimethyladamantane 236 Aqueous Layer 3019
Acetonitrile 236 Drying Loss 42
Sulphuric Acid 472 SS Reactor Output-Stage 1 161
Process water 2278

STAGE-II

Polyethene Glycol 11 Aqueous Effluent 450
Stage I 161 Hyflo 4
Sodium Hydroxide Activated Charcoal 1.0
Process Water
3
SS Reactor Vapour Loss 3
403
Activated Charcoal 1 Output-Stage 2 125
Hyflo 4
583 583
Total Total
STAGE-III
Reactor
Isopropyl Alcohol 103 Recovered IPA 2332
Distilled Isopropyl Alcohol 50 Hyflo + Charcoal Waste 12
Recovred Isopropyl Alcohol 2332 Centrifuge ML 135
Stage 2 125 Drying Loss 8
Activated Charcoal 6 Memantine HCl 100
Hyflo Distillation Loss 35
6
SS Reactor
56. PREGABALIN
Sodium Hydroxide solution in Process water is chilled at 0‐10°C and then charge R‐(‐)‐3-
(Carbamoylmethyl)‐5‐methylhexanoic acid [R‐(‐)‐CMH]. Addition of liquid Bromine is done at
0¬5°C then raise the temperature of the reaction mass up to 30‐35°C. After reaction monitoring,
raise the temperature of the reaction mass to 55‐60°C and apply carbon treatment. The clear
filtrate is then received in another reactor. Excess water is distilled off from the reaction mass.
The reaction mixture is acidified with concentrated Hydrochloric acid. Reaction mass is then up
to 80‐85°C and after that gradual cooling to 25‐30°C. The material is centrifuged after
maintaining of the reaction mass at 25‐30°C for 4‐6 hrs.

The dry material is then charged in IPA and raises the temperature to 80‐85°C. Add DM water
to reaction mass at 80‐85°C. Filter the clear reaction mass and chill it to 8‐12°C. The material is
then centrifuged and dried in under vacuum.
Chemical Reaction:
Material Balance:
STAGE-I
Reactor Output
Compound Qty (KGS) Sr No Compound Qty (KGS)
Spent carbon and
Process water 1417 1 15
hyflo
Sodium Hydroxide 190 2 Spent ML 1982
4‐CMH 137 3 Loss on drying 34
Liquid Bromine 123 SS Reactor 4 Stage1-Output 89
Activated carbon 7
Hyflo 2
Hydrochloric acid 246
STAGE-II
Pregabalin (Stage‐I) 89 1 Spent ML 525
IPA 83 2 Loss on drying 18
Recovered IPA 623 Recovered IPA 623
DM water 470 SS Reactor 3 Pregabalin 100

57. FAMOTIDINE
Stage‐I This stage involves the condensation reaction between ITU and IF in presence of
NaOH, Methanol and Water to give Famotidine Technical, which is leached with methanol to
get Famotidine Crude.
Stage‐II Famotidine Crude in presence of Methanol, Water, Acetic Acid and Ammonia Solution
forms Famotidine API.
Chemical Reaction:

Material Balance:
Input R eactor O utput

ITU 150 M o ther Liquo r 1575
IF 115 Reactio n m ass 140
Caustic Lye
M ethano l
250
50
SS Reactor
W ater 400
Reco vered m ethano l 750

Reactio n m ass 140 Fam o tidine A PI 100
M ethano l 8 M o ther Liquo r Fo r Reco very
797
Reco vered M etahno l 492
A m m o nia 35 So lid W aste 7
A cetic A cid 24 SS Reactor
W ater 200
Charco al 3.00
H yflo 2
Total 904 Total 904

M o ther Liquo r 2372 Reco vered M ethano l 1242
M ethanol
Recovery D istillatio n Residue (W ater)
1130
58. IVABRADINE
Stage‐I:Preparationof3‐(3‐chloropropyl)‐7,8‐dimethoxy‐1,3‐dihydro‐2H‐benzazepin‐2‐one
(Unreduced chloro).
1, 3‐dihydro‐7, 8‐dimethoxy‐2H‐3‐benzazepin‐2‐one (KSM‐I) is reacted with 1‐bromo‐3‐chloro

propane in presence of Potassium tertButoxide in Dimethyl sulfoxide to gives 3‐(3-
chloropropyl)‐7,8‐dimethoxy‐1,3‐dihydro‐2H‐3‐benzazepin‐2‐one (Unreduced chloro).
Stage‐II: Preparation of 3‐(3‐chloropropyl)‐7,8‐dimethoxy‐1,3,4,5‐tetrahydro‐2H‐3-

benzazepin‐2‐one ( Reduced chloro)
Catalytic Hydrogenation of stage‐I in Denatured alcohol with cyclohexane using pd/C gives
3‐(3-chloropropyl)‐7,8‐dimethoxy‐1,3,4,5‐tetrahydro‐2H‐3‐benzazepin‐2‐one ( Reduced chloro).

Stage‐III: Preparation of Ivabradine Hydrochloride Crude
3‐(3‐chloropropyl)‐7,8‐dimethoxy‐1,3,4,5‐tetrahydro‐2H‐3‐benzazepin‐2‐one (stage‐II) is
reacted with (7S)‐3,4‐dimethoxy‐N‐methyl‐bicyclo[4.2.0]octa‐1,3,5‐trien‐7‐methanamine
Hydrochloride (KSM‐II)in presence of potassium carbonate and Sodium iodide in acetone to
gives Ivabradine Hydrochloride Crude.
Stage‐IV: Preparation of Ivabradine Hydrochloride (API).

Ivabradine Hydrochloride recrystallised using methanol and acetone.
Chemical Reaction:

Material Balance:
S T A G E -I
1 ,3 ‐ D ih y d r o ‐ 7 ,8 d i
m e th o x y ‐ 2 H ‐ 3 ,3 87 E fflu e n t 142
B e n z a z a p in
P o ta s s iu m te r t
90
S S R e a cto r E v a p o r a tio n lo s s 1
B u to x id e
1 ‐ B r o m o ‐ 3 ‐ C h lo r o P r o d u c t O u tp u t 118
84
p ro p a n e
S T A G E -II
S ta g e I 118 A q . E fflu e n t 68
H yd ro g e n G a s 25 E v a p o r a tio n lo s s 12
P d /C 5 S S R e a cto r S ta g e II 78
DNS 15 Pd / C 5
R e co v e re d D N S 125 R e co v e re d D N S 125
S T A G E -III
S ta g e II 78 A q . E fflu e n t 104
K S M II 32 E v a p o r a tio n lo s s 11
P o ta s s iu m
55 S S R e a cto r S ta g e III 108
C a r b o n a te
s o d iu m Io d id e 10 C a r b o n D io x id e 12
H y d r o c h lo r ic A c id 60
S T A G E -IV
S ta g e III 108 R e s id u e 13
M e th a n o l 5 E v a p o r a tio n lo s s 5
A c e to n e 5 S S R e a cto r P r o d u c t O u tp u t 100
R e c o v e re d
R e c o v e r e d A c e to n e +
A c e to n e + 90 90
M e th a n o l
M e th a n o l

59. Levitracetam
Stage‐I S(+)‐2‐amino butyramide Hydrochloride reacts with 4‐chloro Butyryl chloride in

presence of Tetra butyl ammonium bromide, potassium hydroxide to give the Levetiracetam
crude (Stage‐I).
Stage‐II Levetiracetam crude is purified by charcoal treatment with Dichloromethane solvent.

Then Dichloromethane is completely distilled out and finally crystallized in Ethyl Acetate to
give the Levetiracetam API.
Chemical Reaction:
O
O
H3C
Cl KOH NH2
H3C NH2 + Cl
N
H2N O
O
Molecular Formula: C 4H10N2O Molecular Formula: C 4H6Cl 2O
Molecular Formula: C8H14N2O2

Material Balance:
SA B A M H C l 115 M o th e r Liq u o r 1209
4CBC 144 So lid W a ste 350
KOH 250
M DC 30 S S R e a cto r
R e co v e re d M D C 970
So d iu m Su lp h a te 50
T o ta l 1559 T o ta l 1559

M o th e r Liq u o r 1209 C ru d e Le v i 180
S S R e a cto r R e co v e re d M D C 970
D istilla tio n Lo ss 59
T o ta l 1209 T o ta l 1209

C ru d e Le v i 180 Fin a l P ro d u ct 100
E th y l A ce ta te 15 R e co v e re d E th y l A ce ta te
285
R e co v e re d E th y l A ce ta te 2 8 5 D istilla tio n Lo ss 15
S S R e a cto r M o th e r Liq u o r 80

60. Valsartan
Biphenyl Valine is reacted with Valeroyl Chloride in presence of potassium carbonate in O-

xylene and Acetone to form Valeroyl Valsartan which is reacted with sodium azide and tri‐n-
butyltin chloride to form TetrazoleValeroyl Valsartan which is reacted with sodium hydroxidein
presence of TBAB to form Valsartan. The Valsartan so formed is precipitated from MDC
bydistilling off excess of MDC and then centrifuging the precipitated slurry. The wet cake
soobtained is further purified in Methylene dichloride by further reflux and maintaining.
Thismass is further Filtered and washed and dried in ANFD and after the necessary inprocess
checks it is packed.

Chemical Reaction:

Material Balance:
Input Output
Acetone 100 Recovered MDC 1650
Hyflow 6 Distillation loss on MDC Rec 100
TBAB 2 Recovered o-xylene 550
Bromine 7 o-xylene recovery loss 35
Carbon 10 tri-n-butyl tin chloride recovery 268
DM Water 2000 recovery loss 10
Sodium Bicarbonate 200 spent carbon 12
Sodium Chloride 43 evaporation loss 54
Valeroyl Chloride 62 effluent 2846
Sodium Azide 67 Valsartan API 100
Sodium Hydroxide 83
Hydrochloric Acid 122 REACTION
Biphenyl Valine 143
Fresh Tri-n-butyl tin chloride 10
Recovered Tri-n-butyl tin chloride 268
Fresh o-xylene 35
Recovered o-xylene 550
Fresh dichloromethane 100
Recovered dichloromethane 1650

61. Irbesartan
Amixtureof1‐(2‐Cyanobiphenyl‐4‐yl)‐methyl‐2‐n‐butyl‐4‐spirocyclopentane‐imidazoline‐5‐one,
Sodium Azide, Triethyl Amine hydrochloride and Toluene were heated for formation of
Tetrazole. Caustic solution was added to it and the product layers were separated and
washedwith Toluene and methyl‐tert butyl ether. Hydrochloric acid was added to the product
layer andpH was adjusted. The product was filtered and solid washed with water. The solid was
dried togive the crude product. The crude product is crystallized from Ethyl Alcohol to give
Irbesartan.

Chemical Reaction:

Material Balance:
Input Output
Acetone 23 Recovered Acetone 441
Recovered Acetone 441
Sodium Chloride 26
Sodium Hydroxide 65 Stage I Evaporation Loss 31
BHD 114 Effluent 1173
4-BMCP 131 Stage I 125
DM Water 970

DM Water 830 Toluene Recovery 412
HCl 69
Stage I 125 Methyl-t-butyl ether rec. 179
Fresh Methy t-butyl ether 9
Recovered Methyl-t-butyl ether 179
Sodium azide 54 Stage II Aqueous Effluent 1191
sodium hydroxide 20 Isbesartan API 100
sodium nitrate 18 Evapration loss 30
toluene 21
Toluene Recovery 412
Triethyl amine hydrochloride 175
62. Fenofibrate
4-chlorophenyl)(4-hydroxyphenyl) Benzophenone is reacted with acetone and chloroform in

presence of sodium hydroxide at reflux temperature to get fenofibric acid (FBR-I).
FBR-I is then converted into its isopropyl ester under reflux condition in presence of
sulfuricacid to yield Fenofibrate.
Chemical Reaction:

Material Balance:
Input Output
(4-chlorophenyl)(4-hydroxyphenyl)
Benzophenone 105 Stage I 98
Acetone 40 Stage I Recovered Acetone 260
Recovered Acetone 260
Caustic Flakes 25 Evaporation Loss 30
Chloroform 60 Effluent 102
Total 490 Total 490

Stage I 98 Fenofibrate API 100
Isopropyl Alcohol 48 Stage Recovered IPA 102
Recovered IPA 102
Sulphuric Acid 30
II Distillation Loss 8
Water 200 Drying Loss 9
Aqueous Effluent 259
Total 478 Total 478
63. Venlafaxine
In an SS reactor are added methanol, cyclohexanone, 4-MEP and KOH. The reaction is refluxed
for 72 hours. On completion of reaction, the material is cooled and centrifuged. The methanol
ML is sent for recovery and reuse. The product is dried and may be sold if client requires. It can
be taken further for next stage.
The reaction is continued in SS reactor by charging methanol, raneyni and stage 1. Using
hydrogen gas pressurised reaction is carried out. Once the reaction is complete Methanol is
recovered and the concentrated mass is transferred to another SS reactor for further processing.
IPA/MDC, formaldehyde and formic acid is added to the mass, followed by sparging of HCL
gas for over 12 hrs. When the reaction is complete recover IPA/MDC. The concentration is then
filtered washed and dried in ANFD. The dried product is unloaded.

Chemical Reaction:
CN
O OH OH
CN
KOH / NH2
Methanol H2 /
+
Raney Nickel
O
Molecular Formula: C6H10O CH3
Molecular Formula: C 9H9NO O O
CH3 CH3
Molecular Formula: C 15 H19NO 2
Formula W eight: 245.31686 Molecular Formula: C15H23NO2
HCHO / HCOOH
OH CH3
N HCl
CH3
Molecular Formula: C 17H28ClNO2

O
CH3
Material Balance:

IPA 25 1 Finished Product 100
MDC 2 Recovered IPA/MDC 175
25
Recovered
175 3 ML 115
IPA/MDC SSR
Formaldehyde 20
Formic Acid 20
Venelafaxine
Stage II 125
Total 390 Total 390

64. Amlodipine Besylate
This stage involve, Benzylidine intermediate preparation by condensation of ethyl 4-[2-(1, 3-

dioxo- 1, 3-dihydro-2H-isoindol-2-yl) ethoxy]-c with 2-chloro benzaldehyde in presence of
piperidine& acetic acid as a catalyst. Benzylidine intermediate further reacted with methyl (2E)-
3- aminobut-2-enoate in acetic acid to form Phthaloyl Amlodipine (Stage 1) which may be sold
as an intermediate. It involves preparation of free base of Amlodipine from Methylamine
solution with DNS (Denatured with Toluene) as a solvent. Free Amlodipine is reacted with
Benzene sulfonic acid with DNS to form crude Amlodipine besylate. Purification of
Amlodipine Besylate crude with DNS as a Solvent is done to get Amlodipine Besylate.
Chemical Reaction:
Stage I: Preparation of phthaloyl amlodipine (Sellable intermediate)


Material Balance:

Ethyl 4-[2-(1,3-dioxo-1,3-dihydro-
2Hisoindol-2-yl)ethoxy]-3- 124 Phthaloyl amlodipine 98
oxobutanoate(EPEA)
2- chloro benzaldehyde 85 Recovered Toluene 1087

Methyl(2E)-3-aminobut-2-enoate 223 SSR Recovered Acetic acid 1540
Toluene 13 Distillation Losses 57
Recovered Toluene 1087
Acetic acid 60
Recovered Acetic acid 1540 Aqueous Waste 750
Water 400

Phthaloyl amlodipine 98 Amlodipine Base 75
Methylamine 155 Effluent 465
Water 275 SSR Recovered Methanol 288
Fresh Methanol 12
Total 828 Total 828

Amlodipine Base 75 Amlodipine Besylate 100
Benzene sulfonic acid 30 Recovered DNS 750
Denatured Spirit 50 GLR Distillation loss 20
Recovered DNS 750 Distillation Residue 35
Total 905 Total 905

65. Trazodone Hydrochloride
Reaction of [1,2,4]triazolo[4,3-a]pyridin-3(2H)-one(TZP) and1-(3-chlorophenyl)-4-(3-

chloropropyl)piperazine.HCl ( T2.HCl) to form Trazodone Crude .Pottasium carbonate is added
to a suspension of TZP in IPA. To the resulting suspensionT2.HCl is added and the entire mass
is reacted at reflux temperature. The resulted TZDBasereacted with excess HCl to give
Trazodone HCl crude.Trazodone Crude to Trazodone HCl.
Trazodone.HCl crude is dissolved in Methanol at refluxing temparature. The reaction massthen

allowed cooling. The solid product is removed by filtration and dried etc.
Chemical Reaction:

Material Balance:

TZP 84 Trazodone Crude 110
T2 Hydrochloride 85 Recovered Methanol 220
Methanol 30 Recovered IPA 285
SSR Distillation Losses 35
Fresh IPA 15 Inorganic Salts 97
Recovered IPA 285
Total 747 Total 747

Trazodone Crude 110 Trazodone Hydrochlorid 100
Methanol 19 Recovered Methanol 428
Recovered Methanol 428 SSR Distillation Loss 24
Total 557 Total 557
66. Paracetamol
To an SS Reactor, is added methanol, p-amino phenol and triethyl amine. To this is added
acetyl chloride. The reaction is refluxed and allowed to complete within 8 hours. On
completion, the reaction is filtered from the centrifuge to collect triethyl amine hydrochloride
which is used to recover TEA. Methanol is then recovered. After about 80% distillation, the
product is filtered from an ANFD and dried.
Chemical Reaction:
OH O OH
+ H 3C Cl
M o le c u la r F o rm u la : C 2H 3C lO
NH2 F o rm u la W e ig h t: 7 8 .4 9 7 6 2
HN
CH3
M o le c u la r F o rm u la : C 6H 6C lN
F o rm u la W e ig h t: 1 2 7 .5 7 1 5 4 O
M o le c u la r F o rm u la : C 8H 9N O 2
F o rm u la W e ig h t: 1 5 1 .1 6 2 5 6

Material Balance:

p-Aminophenol 84 Paracetamol 100
Acetyl chloride 32 Recovered Methanol 330
triethyl amine 3 Recovered Triethyl amine 22
Recovered Triethyl amine 22 SSR
Methanol 70 Distillation Losses 35
Recovered Methanol 330 Aqueous ML 54
Total 541 Total 541
67. AZILSARTAN
Stage‐I:Methyl2‐ethoxy‐1‐[[2’‐(hydroxyamidino)biphenyl‐4‐yl]methyl]‐1H‐benzimidazole‐7¬ca
rboxylate.
Methyl1‐[(2’‐cyanobiphenyl‐4‐yl)methyl]‐2‐ethoxy‐1H‐benzimidazole‐7¬carboxylate (KSM I)
is reacted with hydroxylamine hydrochloride, sodium carbonate in presence of DMSO and
heated to give stage‐I after pouring in process water. Stage‐I is purified by dissolving in mixture
of MDC and aqueous HCl. Pure stage‐I is precipitated by adding aqueous sodium hydroxide
Stage‐II:Methyl1‐[[2'‐(2,5‐dihydro‐5‐oxo‐4H‐1,2,4‐oxadiazol‐3‐yl)biphenyl‐4‐yl]methyl]‐2¬eth
oxy‐1H‐benzimidazole‐7‐carboxylate. Stage‐I is reacted with ethylchloroformate in presence of
potassium carbonate and MDC as a solvent gives stage‐II (in‐situ). It is further cyclized using
O‐Xylene to give stage‐II.
Stage‐III:1‐[[2'‐(2,5‐dihydro‐5‐oxo‐4H‐1,2,4‐oxadiazol‐3‐yl)biphenyl‐4‐yl]methyl]‐2‐ethoxy‐1H
-benzimidazole‐7‐carboxylic acid Stage‐II is hydrolyzed by sodium hydroxide in presence of
THF and water, which on acidification with aqueous HCl gives Stage‐III.
Stage‐IV: AzilsartanMedoxomil A] Stage‐IV (Technical): Stage‐III is reacted with

4‐Hydroxymethyl‐5‐methyl‐1,3‐dioxol‐2‐one, p‐TSCl, and DMAP, K2CO3 in DMAc as a
solvent to give stage‐IV(Technical) after pouring in the process water. B] Stage‐IV: Stage‐IV
(Technical) is purified using mixture of acetone and water.

Stage‐V: Azilsartanmedoxomil mono potassium salt. Stage‐IV is treated with potassium 2‐ethyl
hexanoate in presence of ethyl acetate as a solvent to give potassium salt of
AzilsartanMedoxomil.
Chemical Reaction:


Material Balance:
STAGE-I
KSM 151 Aq. Effluent 168
Hydroxyl Am ine ‐HCI 87 SS Reactor Carbon Dioxide 25
Sodium Carbonate 43 Stage 1 128
DMSO 40
Total 321 Total 321
STAGE-II
Reactor
Stage 1 128 Aq. Effluent 104
ECF 56 SS Reactor Output 122
Pottasium Carbonate 42
Total 226 Total 226
STAGE-III
Sodium Hydroxide 42 SS Reactor Evaporation loss 3
Hydrochloric Acid 102 Output 110
Total 265 Total 265
STAGE-IV

4-hydroxym ethyl-5-m ethyl-
49 Carbon Dioxide 12
1,3-doxol-2-one
p-TSCI 34
SS Reactor Stage 4 113
Pottasium Carbonate 80
Acetic Acid 17
Total 290 Total 290
STAGE-V
Stage 4 113 Effluent 53
SS Reactor Output 100
Pottasium ethyl Hexonate 40
Total 153 Total 153

ANNEXURE-VIII
WATER CONSUMPTION AND WASTEWATER GENERATION
WATER CONSUMPTION
Sr. Category Existing Proposed Total water consumption in

No. water water KL/day
consumption consumption in
in KL/day KL/day
1. Domestic 3 5 8
2. Industrial
2.1 Process & 18 92 110
Washing
2.2 Cooling 6 9 15
2.3 Boiler 8 10 18
3 Gardening 0 2 2
Total (Industrial) 32 113 145
Total (Domestic + 35 118
153
Industrial)
WASTEWATER GENERATION
Sr. Category Existing Proposed waste Total waste water

No. waste water water generation generation in KL/day
generation in KL/day
KL/day
1. Domestic 3 4 7
2. Industrial
2.1 Process & 12+4.5 97 113.5
Washing
2.2 Cooling 2 1 3
2.3 Boiler 3 2 5
3. Others 0
(Gardening)
Total 21.5 100 121.5
(Industrial )
Total 20.11 104 128.5
(Domestic +
Industrial )

PROPOSED WATER BALANCE DIAGRAM
G.I.D.C (153KL/day)
Process&Washing Boiler Cooling Domestic Gardening

110 KL/day 18 KL/day 15 KL/day 8 KL/day 2 KL/day
Loss Loss
Effluent 13 KL/day 12 KL/day
113.5 KL/day
Blow Down Blow Down
5 KL/day 3 KL/day
Septic Tank
7 KL/day
E.T.P
121.5 KL/day
C.E.T.P
121.5 KL/day

ANNEXURE-IX
DETAILS OF EFFLUENT TREATMENT PLANT
EXISTING EFFLUENT TREATMENT PLANT

The effluent of 1.2 KLD is treated in unit’s own effluent treatment plant consisting of neutralization
and equalization and then it is passed through filter press and the treated effluent is sent to CETP.
PROPOSED EFFLUENT TREATMENT PROCESS DESCRIPTION
THEORY OF HYDRODYNAMIC CAVITATION
Hydrodynamic cavitation describes the bubble generation, bubble implosion and process of
vaporization, which occurs in a flowing liquid as a result of a decrease and subsequent increase in
pressure. In pipe systems, cavitation typically occurs either as the result of an increase in the kinetic
energy (through an area constriction).
The process of bubble generation, and the subsequent growth and collapse of the cavitation bubbles,
results in very high energy densities and in very high temperatures and pressures at the surface of the
bubbles for a very short time. The overall liquid medium environment, therefore, remains at ambient
conditions. Controlled cavitation can be used to enhance chemical reactions or propagate certain
unexpected reactions because free radicals are generated in the process due to disassociation of vapors
trapped in the cavitating bubbles.
Orifices and venturi are reported to be widely used for generating cavitation. A venturi has an inherent
advantage over an orifice because of its smooth converging and diverging sections, such that that it can
generate a higher velocity at the throat for a given pressure drop across it.
This is also used in the mineralization of bio-refractory compounds which otherwise would need
extremely high temperature and pressure conditions since free radicals are generated in the process due
to the dissociation of vapors trapped in the cavitating bubbles, which results in either the intensification
of the chemical reaction or may even result in the propagation of certain reactions not possible under
otherwise ambient conditions.
Hydrodynamic cavitation can also improve some industrial processes. For instance, cavitated corn
slurry show higher yields inethanolproduction compared to uncavitated corn slurry in dry milling
facilities.

Consider the case of a Venturi as shown in Figure above. At low flow rate, water is everywhere free of
cavitation. Velocity is maximum in the section of minimum area and pressure is then minimum. When
the flow rate is progressively increased, the minimum pressure decreases and there will be a critical
flow rate for which the vapor pressure is obtained at the throat. At this operating point, cavitation
appears in the section of minimum area. In Figure above, two bubbles are clearly visible in the upper
part of the Venturi. This is the start of the cavitation state. If the flow rate through the Venturi is further
increased, the extent of cavitation also increases. Figure given above gives an example of developed
cavitation in the same Venturi device. Many vapor structures which are different from single bubbles
are visible.
At this point the chlorine when injected will oxidise the organic matter exploded bubble and due to the
large surface area available, the oxidation by chlorine molecule is almost instantaneous.

Treatment Process:
The setup for the hydrodynamic cavitation reactor is given in the figure below:
The waste water is equalised over organic matter and flow. The pH of the waste water is raised to 10.5
by hydrated lime and filtered. The waste water is then pumped through a venturi. At the suction side,
chlorine is injected to achieve hydrodynamic cavitation. This is a batch process and the system is kept
under recirculation till the COD is reached to desired limit. This is again filtered in the filter press and
the filtered waste water is sent for electrolysis.
ETP FLOW DIAGRAM
Collection Flocculation Primary Hydrodynamic

Tank tank Settling Cavitation Tank
Tank
CETP Guard
Tank

DETAILS OF DIFFERENT ETP UNITS
Sr. Name of Unit No of Unit Capacity

No.
1 Collection Cum Equalization Tank 1 10 KL
2 Flocculation Channel/Tank 1 5 KL
3 Primary Settling Tank 1 5 KL
4 Hypochloride dosing tank 1 20 KL
7 Guard Tank 1 30 KL
EFFLUENT QUALITY BEFORE TREATMENT & AFTER TREATMENT IN ETP
Sr. Category Before After After After

No. of Waste Treatment Primary Hypochlori Carbon
Water Treatment de Dosing Filter
1. pH 3 to 6 6.5 to 7.5 6.5 to 7.5 6.5 to 7.5
2. COD (mg/l) 3000-4000 800-1000 100-250 30-100
3. BOD (mg/l) 350-450 100-250 30-50 10-30
4. TDS (mg/l) 4000-5000 4000-5000 5000-6000 5000-
6000
5. Ammonical 30-50 30-50 10-20 10-20
Nitrogen
(mg/l)
6. TSS (mg/l) 150-200 50-60 70-80 10-20

ANNEXURE-X
DETAILS OF FUEL AND ELECTRICITY
Sr.
Particulars Existing Proposed Total Remark
No.
Will be met through
1. Electricity 300 HP 500 HP 800 HP
MGVCL company
Natural Gas: Natural Gas
Natural Gas: 220
Natural Gas: 160
SCM/hour Supplied by Adani
2. Boiler ( 2 Nos) 60 SCM/hour SCM/hour
Bio coal: 350
Fire Wood: Bio coal: 300 Bio coal: Vitality
50 kg/hour kg/hour
kg/hour Bio Coal
Thermo pack
Bio Coal Bio Coal Bio coal: Vitality
3. (5 lac None
200 Kg/Hr 200 Kg/Hr Bio Coal
Kcal/hour)
4. HSD - 40 Lit/Hr. 40 Lit/Hr. Local Dealer

ANNEXURE-XI
FLUE GAS AND PROCESS GAS EMISSIONS
FLUE GAS EMISSIONS
Sr. Stack Stack Type of Fuel Type Permissi APCM

No. Attached To Height Fuel Consumption of ble Limit
(M) Emissi
on
EXISTING As Per CCA No.-AWH-84183
1. Boiler 11 Natural 60 SCM/hour SPM 150 --
Gas mg/NM3
2. Boiler 11 Fire 50 kg/hour SO2 100 PPM Cyclone
Wood NOx 50 PPM Seperator
Proposed
1. Boiler 30 Natural 220 SCM/hour SPM 150 --
Gas mg/NM3
2. Boiler 30 Bio Coal 350 kg/hour SO2 100 PPM Multi Dust
NOx 50 PPM Collector
3. D.G. Set 11 HSD 40 Lit / Hr SPM 150 --
mg/NM3
SO2 100 PPM
NOx 50 PPM
PROCESS EMISSION
Sr. Stack Attached To

Stack Probable Permissible APCM
No. Height In Pollutant Limit
Meter Emission
EXISTING As Per CCA No.-AWH-84183
1. Lead Bonded 11 HCl 20 mg/Nm3 HDPE Alkali
Vessel Scrubber
2. Glass Lined Vessel 11 HCl 20 mg/Nm3 HDPE Alkali

(Chlorination and HBr 30 mg/ Nm3 Scrubber
Bromination)
PROPOSED
1. Reactor No 212 11 NH3 Acid Scrubber
2 All Reactors 11 SO2 Water Venturi
HCl Scrubber Followed
Cl2 By Alkali Scrubber
Br2
HBr

ANNEXURE-XII
DETAILS OF HAZARDOUS WASTE
Sr. Type of Category Existing Proposed Total Method Of Disposal

No. Waste CCA No.- Quantity Quantity
AWH-84183 per Year per Year
Quantity
Per Year
1. ETP 35.3 662 MT/Year 4933 5595 Disposal at TSDF of
Sludge MT/Year MT/Year Nandesari
Environment Control
Ltd. (NECL)
2. Discarded 33.3 31.68 36.60 68.28 Decontamination
Containers MT/Year MT/Year MT/Year within company
premises
3. Spent 28.3 -- 37MT/Year 37 Disposal at CHWFI

carbon MT/Mont for incineration
h facility
4. Distillation 20.3 25.2 2730.12 2755.62 Disposal at CHWFI
residue MT/Year MT/Year MT/Year for incineration
facility
5 Spent Oil 5.1 0.72 MT / 0.83 MT / 1.55 Disposal By Sending
Year Year MT/Year to Registered Refiners

ANNEXURE-XIII
DETAILS OF HAZARDOUS CHEMICALS
Sr. Name of Chemical

No.
1 Sodium Hydroxide
2 Acetone
3 Tartaric Acid
4 Sulphuric Acid
5 Isopropyl alcohol
6. Trifluoroacetic Acid
7. Hydroxy ethyl morpholine
8. Isopropyl Trifluoroacetate
9. Acidic acid
10. Toluene
11. Furmaric Acid

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M/S. KALKI CHEMICALS INDUSTRIES. GIDC NANDESARI, VADODARA.

PROPOSED TERMS OF REFERENCE

 Standard TOR of MoEF&CC for organic sector will be followed.

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd.11

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd.12

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd.13

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd.14

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M/s. Jyoti Om Chemical Research Centre Pvt. Ltd.16

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LIST OF EXISTING & PROPOSED PRODUCTS AND THEIR PRODUCTION CAPACITY

Sr. Product Name Existing Proposed Total

11. 2-chloro ethyl morpholine HCl 0 15 15

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd.18

Sr. Product Name Existing Proposed Total

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd.19

Sr. Product Name Existing Proposed Total

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd.20

Sr. Name Of Residential Address Mobile No.

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd.21

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd.22

LIST OF PROPOSED RAW MATERIALS

Sr. Name of Product Production Name of Raw material Raw

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Sr. Name of Product Production Name of Raw material Raw

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Sr. Name of Product Production Name of Raw material Raw

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Sr. Name of Product Production Name of Raw material Raw

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Sr. Name of Product Production Name of Raw material Raw

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Sr. Name of Product Production Name of Raw material Raw

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Sr. Name of Product Production Name of Raw material Raw

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BRIEF MANUFACTURING PROCESS