Claims
- 1. A process for preparing a calcium salt of a statin having the formula:
- 2. The process of claim 1, wherein R is an organic radical from a statin selected from the group consisting of pravastatin, fluvastatin, cerivastatin, atorvastatin, rosuvastatin, pitavastatin, simvastatin and lovastatin.
- 3. The process of claim 2, wherein the statin is selected from the group consisting of atorvastatin, rosuvastatin, pitavastatin and simvastatin.
- 4. The process of claim 3, wherein the statin is rosuvastatin.
- 5. The process of claim 3, wherein the statin is pitavastatin.
- 6. The process of claim 3, wherein the statin is simvastatin.
- 7. The process of claim 3, wherein the statin is atorvastatin.
- 8. The process of claim 1, wherein the process is carried out in a mixture of water and a C1 to a C4 alcohol.
- 9. The process of claim 1, wherein the contacting is at elevated temperature.
- 10. The process of claim 1, wherein the contacting takes place in the presence of a phase transfer catalyst.
- 11. The process of claim 1, further comprising a step of recovering the calcium salt of the statin.
- 12. The process of claim 1, wherein R2 and R3 are both hydrogen.
- 13. The process of claim 1, wherein R4 is hydrogen.
- 14. The process of claim 1, wherein at least one of R2 or R3 is a trialkylsilyl protecting group.
- 15. The process of claim 1, wherein R4 is a trialkylsilyl protecting group
- 16. The process of claim 1, further comprising a preliminary step of contacting the ester derivative, wherein the ester derivative has at least one protecting group, with an acid catalyst to hydrolyze the protecting group.
- 17. The process of claim 16, wherein the ester derivative has the formula:
- 18. The process of claim 17, wherein R is an organic radical from atorvastatin.
- 19. A pharmaceutical composition comprising the statin salt prepared by the process of claim 1 and a pharmaceutically acceptable excipient.
- 20. A process for preparing rosuvastatin calcium salt comprising contacting a C1 to a C8 ester of 7-[4-(4-fluorophenyl)-6-iso-propyl-2-(N-methyl-N-methylsulfonylamino)pyrimidin-5-yl]-(3R,5S)-dihydroxy-(E)-6-heptenoate with a sufficient amount of calcium hydroxide.
- 21. A process for preparing rosuvastatin calcium salt comprising contacting lactone form of rosuvastatin with a sufficient amount of calcium hydroxide.
- 22. A process for preparing pitavastatin calcium salt comprising contacting a C1 to a C8 ester of (E)-3,5-dihodroxy-7-[4′-(4″-fluorophenyl)-2′-(1″-cyclopropyl)-quinolin-3′-yl]-hept-6-enoate with a sufficient amount of calcium hydroxide.
- 23. A process for preparing pitavastatin calcium salt comprising contacting lactone form of pitavastatin with a sufficient amount of calcium hydroxide.
- 24. A process for preparing a calcium salt of a statin having the formula:
- 25. The process of claim 24, wherein R is an organic radical from a statin selected from the group consisting of pravastatin, fluvastatin, cerivastatin, atorvastatin, rosuvastatin, pitavastatin, simvastatin and lovastatin.
- 26. The process of claim 25, wherein the statin is selected from the group consisting of atorvastatin, rosuvastatin, pitavastatin and simvastatin.
- 27. The process of claim 26, wherein the statin is rosuvastatin.
- 28. The process of claim 26, wherein the statin is pitavastatin.
- 29. The process of claim 26, wherein the statin is simvastatin.
- 30. The process of claim 26, wherein the statin is atorvastatin.
- 31. The process of claim 24, wherein R2 and R3 are both hydrogen.
- 32. The process of claim 24, wherein R4 is a hydrogen.
- 33. The process of claim 24, wherein at least one of R2 or R3 is a trialkylsilyl protecting group.
- 34. The process of claim 24, wherein R4 is a trialkylsilyl protecting group.
- 35. The process of claim 24, further comprising a preliminary step of contacting the ester derivative, wherein the ester derivative has at least one protecting group, with an acid catalyst to hydrolyze the protecting group.
- 36. The process of claim 35, wherein the ester derivative has the formula:
- 37. The process of claim 36, wherein R is an organic radical from atorvastatin.
- 38. The process of claim 24, wherein the mixture of water and the alcohol is from about a 5% to about a 20% mixture of water and alcohol (v/v).
- 39. The process of claim 24, further comprising adding a phase transfer catalyst to the mixture of step (a).
- 40. The process of claim 24, wherein the mixture is heated from about 40° C. to about 70° C.
- 41. The process of claim 24, further comprising a filtering step between steps (b) and (c).
- 42. The process of claim 24, wherein precipitating occurs by addition of water.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit of provisional application Serial No. 60/312,812, filed Aug. 16, 2001 and U.S. patent application Ser. No. 10/037,412, filed Oct. 24, 2001, which claims the benefit of provisional application Serial No. 60/249,319, filed Nov. 16, 2000, all of which are incorporated herein by reference.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60312812 |
Aug 2001 |
US |
Divisions (1)
|
Number |
Date |
Country |
Parent |
10222556 |
Aug 2002 |
US |
Child |
10803414 |
Mar 2004 |
US |