Process for the preparation of prostaglandin derivatives

• US 7,166,730 B2
• Filed: 05/10/2005
• Issued: 01/23/2007
• Est. Priority Date: 01/27/2000
• Status: Expired due to Term

• Current Assignee: FineTech Pharmaceutical Ltd. (RxElite, Inc.)
• Original Assignee: FineTech Laboratories Ltd. (RxElite, Inc.)
• Inventors: Pertsikov, Boris, Gutman, Arie, Nisnevich, Gennady, Etinger, Marina, Zaltzman, Igor, Yudovich, Lev, Tishin, Boris
• Primary Examiner(s): Carr; Deborah D.
• Application Number:
  US11/125,164
• Publication Number:
  US 20050209337A1
• Time in Patent Office: 623 Days
• Field of Search: 554/222, 554/142, 554/159, 554/221
• US Class Current: 554/159
• CPC Class Codes: C07C 2601/08 the ring being saturated
• CPC Class Codes: C07C 405/00 Compounds containing a five-membered ring having two side-chains in ortho position to each other, and having oxygen atoms directly attached to the ring in ortho position to one of the side-chains, one side-chain containing, not directly attached to the ring, a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, and the other side-chain having oxygen atoms attached in gamma-position to the ring, e.g. prostaglandins ; Analogues or derivatives thereof
• CPC Class Codes: C07D 307/935 Not further condensed cyclopenta [b] furans or hydrogenated cyclopenta [b] furans

Abstract

The invention provides a novel process for the preparation of prostaglandins and analogues thereof, and new crystalline intermediates in the process.

Claims

1. A process for the preparation of alkyl 5Z-prostenoates of formula [1]

7. A process according to any one of claims 1 and 2 wherein R¹ is methyl or isopropyl.

8. A process according to any one of claims 1 and 2 wherein Y is bromide or iodide.

9. A process according to any one of claims 1–

5 wherein R² is benzoyl, p-toluoyl, p-chlorobenzoyl, p-bromobenzoyl or p-phenylbenzoyl (PPB).

10. A process according to any one of claims 1, 2, 4 and 5 wherein R³ is tetrahydro-2H-pyran-2-yl or t-butyldimethylsilyl group.

2. A process for the preparation of alkyl 5Z-prostenoate of formula [1]

3. A process for the preparation of lactol of formula [4]

4. A process for the preparation of compound of formula [6]

6. A process according to claim 4 which process comprising the steps of converting compound [9-2] into compound [9-1], oxidizing the hydroxyl group of the compound [9-1] to yield the compound [6] and recycling the compound [6] to the beginning of the process.

5. A process for the preparation of compound

11. A process according to claim 5 wherein said stereoselective reduction of the carbonyl group of the compound [6] is carried out by (−

)-B-chlorodiisopinocampheylborane.

12. A process according to claim 5, which further comprises purifying the compound of formula 5 [X=(α

-OR³, H)] by re-crystallization.

13. A process for the preparation of compound of formula [5] [A=—

CH₂CH₂—

;

X=(α

-OR³, H)]

14. A process according to claim 13 wherein said catalyst comprises palladium, platinum or nickel.

15. A process according to claim 13 wherein said catalyst is palladium on carbon.

16. (3aR,4R,5R,6aS)-4-[3S-(t-Butyldimethylsiloxy)-5-phenyl-1E-pentenyl]-5-(4-phenylbenzoyloxy)-hexahydro-2H-cyclopenta[b]furan-2-one of the formula

17. Crystalline MTBE solvate of (3aR,4R,5R,6aS)-4-[3S-(t-butyldimethylsiloxy)-5-phenyl-1E-pentenyl]-5-(4-phenylbenzoyloxy)-hexahydro-2H-cyclopenta[b]furan-2-one.

18. Crystalline (3aR,4R,5R,6aS)-4-[3R-(t-butyldimethylsiloxy)-4-[3-(trifluoromethyl)phenoxy]-1E-butenyl]-5-(4-phenylbenzoyloxy)-hexahydro-2H-cyclopenta[b]furan-2-one of the formula

19. Crystalline (3aR,4R,5R,6aS)-4-[3R-(t-butyldimethylsiloxy)-4-[3-(trifluoromethyl)phenoxy]-1E-butenyl]-5-hydroxy-hexahydro-2H-cyclopenta[b]furan-2-ol of the formula

20. (3aR,4R,5R,6aS)-4-[3S-(t-Butyldimethylsiloxy)-5-phenyl-1E-pentenyl]-5-hydroxy-hexahydro-2H-cyclopenta[b]furan-2-ol of the formula

21. Crystalline (3aR,4R,5R,6aS)-4-[3S-(t-butyldimethylsiloxy)-5-phenyl-1E-pentenyl]-5-hydroxy-hexahydro-2H-cyclopenta[b]furan-2-ol.

22. Crystalline (3aR,4R,5R,6aS)-4-[3R-(t-butyldimethylsiloxy)-5-phenylpentyl]-5-hydroxy-hexahydro-2H-cyclopenta[b]furan-2-ol.