Calcium Acetate → Atorvastatin

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. Ethyl acetate was taken in another RBF and was treated with 30 mg of L-lysine or L-argenine. The organic layer was further 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 atorvastatin amorphous. The product thus obtained was humidified under nitrogen atmosphere to obtain stable atorvastatin amorphous calcium with 5-6% water w/w.

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. additionwas treated with 30 mg of L-lysine or L-argenine
16. additionThe organic layer was further treated with butylated hydroxy toluene
17. distillationThe organic phase was then distilled
18. customto remove ethyl acetate completely till powder or lump of material
19. customwas obtained
20. customThe solid thus obtained
21. stirringstirred for 30 min
22. filtrationThe product was filtered
23. washwashed with cyclohexane
24. customdried at 30° C. to 35° C
25. additionThe partially dried wet cake was treated with diethyl ether
26. customto obtain slurry
27. filtrationThe slurry was filtered
28. customdried

ORD record

ord-2a0cceae449a41d6b8f500c30c37cc3c

Source dataset

uspto-grants-2012_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08115015B2