LOSARTANPOTASSIUM

Stee Cano 4 Brome Methyl Biphem

1Cyano Methylbipheny1(01THN) 1006

ADhromo 5,5 Dimethy! Hidinatoin (DD) 92Kg
An Bie sobutiro Nitrile

MethylenChoride sookg

n-Hexane 2001s

Ssodium Bicarbonste K

Erocedure

lean and heck the Reactor (lR

harg Methylene Chlorde st RI
hary 2 (yano 4 MethylBiphenyl at RI
harge DDH at RI
Char1:o Bis Isobutironitrile at R1
Heat hur
Manla reflux for 24 Hn
heck IPI after 24Hrs O1BN below 5%
Afler reaction completed ( harge watcr 250 Lis
 10 Stir for 10 min and settle for 30 min.
Separate top Layer
Charge5% solution of Sodium Bicarbonate solution.
13 Stir for 10 min and settle for 30 min.
14 Separate top Layer.
15 Charge water 250 Lts.
16 Stir for 10 min and settle for 30 min.
17 Separate top Layer.
18 Suck Methylene Chloride in to Rector and distilled of completely. finally use
vacuum.
19 Charge n-Hexane at RT.
20 Stir for 1 Hr at RT.
21 Centrifuge and wash with n-Hexane.
22 Dry at 50-55C at Tray Drier

Dry Wt: 135Kgs

HPLC: 90%
Mr.: 95-105
 Sage-l: 2-1-Butnl-4-Chloro-5-Hydroxy methyl-1-12 Cyano Biphenyll
Imidazole.

1. Stage-1 100Kgs
2 Toluene 600Lts

3. Water 200Lts

Caustic Soda flaks

19.1Kg and 10Kg

5 2 Butyl 4 Chloro 5 formyl Imidazole

68Kgs
Tetra Butyl Ammonim Bromide
7Ke
Sodium Boro Hydride:
SKgs
Methanol 50Lts

9 Sodium Meta Bisulphite

5Kgs

Procedure:
Clean and Check the reactor SSR.
Charge water and Caustic Soda Flaks 19.1 Kg at RT
 Stir for 20 min, Check Clear Solution.
Charge 2 Butyl 4Chloro 5 Formyl Imidazole at RT
Stir for 20 min, Check Clear solution and
precipitate immediately
. Charge l etra Butyl Ammonium Bromide at RT.
Charge 1Toluene at RT.
Cool to 20C
Charge Stage-I at 20C,
10 Stir for 16 to 18 Hrs at 20C
11 Check HPLC, Stage-I below 5%.
12. Settle for 20 min. Separate two Layers.
13 Take Toluene Layer and wash with 200Lts water and 10 Kgs Caustic Soda
Flaks solution.
14 Take Toluene Layer wash with 5% Sodium Meta Bisulphite solution.
15 Take Toluene Layer and wash with 200Lts x 2 times.
16 Take Toluene Layer Filter through Nutch.
17 Take Filtrate and Add Sodium Boro Hydride at RT.
18 Stir for 1Hr at RT.
19 Heat to 40C.
20 Slowly add Methanol at 40C.
21 Stir for 3Hrs at 40C.
22 Slowly add water 200Lts at 40C.
23 Cool to RT.
Stir for 1Hr at RT.
25 Cool to 155C.
Stir for 1Hr at 15C.
26 and finally wash with water.
27 Centrifuge and wash with Toluene 30Lts
28 Spin Dry about 2Hrs.
Dry at 75C to 80C at Tray Drier
29

Dry Wt: 101 to 105SK

99% above.
HPLC
Mr: 157-160C
 SOgc-lll n-Buyl-4-Chloro-5- Hydroxy methyl-1-I2-11-tetrazole-5ylo
Biphenyl-4-l methylllmidizole.

Stage-1: 100Kgs
Toluene 400Lts

n-Methyl pyrrolidinone 100Lts

Sodium Azide 68Kgs

Tri Ethyl Hydrochloride 144Kgs

Caustic Soda Flaks 50Kgs

Methylene Chloriode 100Lts

Carbon 5Kgs

Sodium Hydro Sulphite 10Kgs

10 Sodium Meta Bisulphate SKes
. Acetic Acid 100Lts

12.
12 Iso Propyl Alcohol 90Lts

13. Hyflow
Oedtre
Clean and Check the
reactor SSR
Charge Toluene at RI
Charge n-Methy! Pirrolidinone at R1
Charge Stage-1ll at RT
Charge Sodium Azide at RT
Charge 7ri Fthyl lydrochloride at RT
Heat to 90-950
Stur for 30 Hrs at 90-95C
Check HPLC. Stage-II below 5%.
10 Cool to RT
11 Charge 2501ts water and 5OKgs Caustic Soda Flaks solution
12 Stir for 30 min and Settle for 30 min.
at RT
13 Separate Two Layers.
14 Toluene Layer Kept aside.
Take Middle Layer and Bottom Layer and
charge Toluene 100Lts
16 Stir for 30 min and Settle for 30 min.
17 Separate Two Layers.
18 Toluene Layer Kept aside.
19 Take Middle Layer and Bottom
Layer and charge Toluene 100Lts
20 Stir for 30 min and Settle for 30 min.
21 Separate Two Layers.
22 Toluene Layer and bottom Layer Kept aside.
Take Middle Layer and charge Water 400Lts
atRT
24 Stir for 30 min at RT.
25 Charge Methylene Chloride at RT
26 Stir for 30 min at RT.
21 Reaction Mass Pass through nutch
28 Take Filtrate and Settle for 30 min
29 Separate two Layers.
30 Take Top Layer and Sodium Hydro
Sulphite and Carbon
31 Heat to 50C
at RT
32 Stir for 1Hr at 500
33 Reaction Mass Filter through L.eaf Filter at
50C
34 Fake Tilirute
Coof to 200 andCool to RI
36 Ph
adjusted to 4. to 4.3 with 1:1 Dilute Acetic Acid
31 Sur tor 8Hrs at 20C.
entrifuge and wash with water50Lts.
39 Take wet Cake and
charge 100L ts water
Stir for 1Hr at RT
41 Centriiuge and wash with 20 Ls water
Spin Dry for 3Hrs in Centrifuge
43 Charge Wet Cake and Charge Iso Propyl Alcohlo 80Lts at RT
44 Heat to 50C
A Stir for 20 min at
50C
A6 Cool to RT
41 Centrifuge and wash with Iso Propyl alcohol 1OLts
48 Spin Dry over a period of 4 to SHrs
49 Dry at 60-65 at Tray Drier

Dry Wt: 85-90Kgs

HPLC: 9% above
HPLC Assay: 98% to 102%
S Ash: below 0. 1%
C Assay: 98% to 102%
Mr: 182C to 184.5C
Pharmu:
LOSARTAN POTASSIUM4
1.
Stage-1II
50Kgs
Methanol
200Lts and 25Lts
Potassium Hydroxide Pellets
6.75Kgs
Carbon
2Kgs
Acetone 50Lts,50Lts and 200Lts.

Procedure:

Clean and Check the reactor SSR.

Charge Methanol at RT. Check Mc:0.1% below.
3 Charge Potassium Hydroxide Pelets at RT.
A Stir for 30 min, Check Clear solution.
Charge Stage-Ill at RT.
Ph adjusted to 9.0 to 9.5 with CP Pellets in Methanol at RT
Heat to reflux.
8 Stir for 1Hr at reflux
9. Charge Carbon at 50C.
10 Stir for 1Hr at reflux.
11. Filter through Leaf Filter at 50C
12. Distilled of Methanol Completely Under High Vaccum up to SOC.
harye 1 s an listlled nt completely under Vacuum at below 50
ctone and dhstulled ofcompletely under Vacuurm at helow

harycH 1cetone al S0
S n at Si
foRI
Str for 11ir at RI
Sr for r a t 0-S
Ctrafuge and wash with chilled acetone
10Lts
pn Dr over a Period of 3Hrs
i a d in to a Carboy and Dry
Dry at 60-650 at Tray Drier

Dry Wt: 9OKgs

above 99%
HPLC:
102%
HPLC Assay: 98 to
8.4 to 9.2
Ph Range:
Below 19%
MC:
/niermedinie: Tri Lty Hydroriloride

ri tyi Antine
100Kgs
Tolene 200Lts

ilydrochioride 'p Grade 120Lts

Procedure:

Clean and Check the Reactor GLR.

Charge Toluene at RI
Charge Tri Ethyl Amine al RT. temperature at
with Controlling the
Slowly add Hydroclhloric acid using Siphon
below 50C
Alier HCI addition completed Check Ph
on paper it should be acetic.
Stir for 30 min at 50C.
Heat to Azco tropical reflux.
Maintain at rellux up to water collection completed.
below 0.5%.
9. After completion of water collection Check Mc
10. Cool to RT.
11. Stir for 2Hrs at RT.
12 Centrifuge and wash with toluene 20Lts.
13 Dry at 70 to 80C in Tray Drier.

Material is highly Hygroscopic. So Packing should be under Nitrogen

Note:
Dry Wt: 135Kgs
C Assay: 98- 102o