Calcium Acetate → Atorvastatin calcium

20 gm of R—(R*,R*)]-1,1-dimethylethyl-2-(4-fluorophenyl)-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino) carbonyl]-1H-pyrrole-1-heptanoate was taken in 400 mL of acetonitrile to obtain clear solution at 40° C. to 45° C. The reaction mixture was cooled to 25° C. to 30° C. and 2.60 gm of NaOH solution in 100 mL of water was added within 15 min and stirred for 30 min. Acetonitrile was distilled under vacuum to obtain white slurry or solid. The compound thus obtained was further cooled at 10° C. to 15° C. 400 mL of water was added followed by slow addition of 400 mL of ethyl acetate to dissolve the solution. 10.46 gm of calcium acetate solution in 244 mL of water was added to obtain hazzy solution at 10° C. to 15° C. The reaction mixture was stirred for 2 hrs at 35° C. to 40° C. and cooled to 30° C. to 35° C. The organic layer was separated and washed with water and filtered through hyflow bed followed by washing with ethyl acetate. The organic layer was treated with butylated hydroxy toluene. The organic phase was then distilled to remove ethyl acetate completely till powder or lump of material was obtained. The solid thus obtained was treated with 100 mL of cyclohexane and stirred for 30 min. The product was filtered, washed with cyclohexane and dried at 30° C. to 35° C. The partially dried wet cake was treated with diethyl ether to obtain slurry. The slurry was filtered and dried to get stabilized atorvastatin amorphous.

1. customto obtain clear solution at 40° C. to 45° C
2. temperatureThe reaction mixture was cooled to 25° C. to 30° C.
3. distillationAcetonitrile was distilled under vacuum
4. customto obtain white slurry or solid
5. customThe compound thus obtained
6. temperaturewas further cooled at 10° C. to 15° C
7. dissolutionto dissolve the solution
8. customto obtain hazzy solution at 10° C. to 15° C
9. stirringThe reaction mixture was stirred for 2 hrs at 35° C. to 40° C.
10. temperaturecooled to 30° C. to 35° C
11. customThe organic layer was separated
12. washwashed with water
13. filtrationfiltered through hyflow bed
14. washby washing with ethyl acetate
15. additionThe organic layer was treated with butylated hydroxy toluene
16. distillationThe organic phase was then distilled
17. customto remove ethyl acetate completely till powder or lump of material
18. customwas obtained
19. customThe solid thus obtained
20. stirringstirred for 30 min
21. filtrationThe product was filtered
22. washwashed with cyclohexane
23. customdried at 30° C. to 35° C
24. additionThe partially dried wet cake was treated with diethyl ether
25. customto obtain slurry
26. filtrationThe slurry was filtered
27. customdried
28. customto get

ORD record

ord-bebc82ce1def4e02972d4136ad910ddd

Source dataset

uspto-grants-2012_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08115015B2