Claims
- 1. A process for the preparation of isocoumarin derivatives of the formula
- 2. The process of claim 1, wherein R3 is an electron withdrawing group selected from the group consisting of aryl, hetroaryl, sulfonate, phosphonate, cyano, —CO2R7, wherein R7 is C1-C6 alkyl, and —COR8, wherein R8 is a halogen.
- 3. The process of claim 1, wherein R3 is —CO2C2H5.
- 4. The process of claim 1, wherein X is —OCH3.
- 5. The process of claim 4, wherein n is 2.
- 6. The process of claim 1, wherein Y is an acyl activating substituent selected from the group consisting of halogen, imidazoyl, pyridyl and aryloxy.
- 7. The process of claim 6, wherein said halogen is chloro, bromo or iodo.
- 8. The process of claim 1, wherein Y is imidazoyl.
- 9. The process of claim 1, wherein said solvent is an aprotic solvent.
- 10. The process of claim 9, wherein said aprotic solvent is a halogenated or ethereal solvent.
- 11. The process of claim 9 wherein said aprotic solvent is acetonitrile or N-methyl pyrrolidinone.
- 12. The process of claim 1, wherein said base is selected from the group consisting of tertiary amine, amidine, amide and tertiary alkoxide bases.
- 13. The process of claim 1, wherein said base is triethylamine.
- 14. The process of claim 1, wherein said base is 1,8-diazabicylco[5.4.0]-undec-7-ene.
- 15. A process for the preparation of isocoumarin derivatives of the formula:
- 16. The process of claim 15, wherein Y is an acyl activating group selected from the group consisting of halogen, imidazoyl, pyridyl and aryloxy.
- 17. The process of claim 16, wherein said halogen is chloro, bromo or iodo.
- 18. The process of claim 15, wherein Y is imidazoyl.
- 19. The process of claim 15, wherein said solvent is an aprotic solvent.
- 20. The process of claim 19, wherein said aprotic solvent is a halogenated or ethereal solvent.
- 21. The process of claim 19, wherein said aprotic solvent is acetonitrile or N-methyl pyrrolidinone.
- 22. The process of claim 15, wherein said base is selected from the group consisting of tertiary amine, amidine, amide and tertiary alkoxide bases.
- 23. The process of claim 15, wherein said base if triethylamine.
- 24. The process of claim 15, wherein said base is 1,8-diazabicylco[5.4.0]-undec-7-ene.
- 25. The process of claim 15, wherein R11 is methyl, R12 is ethyl, and R9 and R10 are methoxy and said isocoumarin derivative is:
- 26. The process of claim 25, further comprising removal of the ethyl ester group and a methyl group from said isocoumarin derivative:
- 27. A process for the preparation of homophthalate derivatives of the formula:
- 28. The process of claim 27, wherein said homophthalate derivative of the formula:
- 29. The process of claim 27, wherein said strong base is lithium diisopropylamide or lithium tetramethylpiperidide.
- 30. The process of claim 27, wherein said solvent is tetrahydrofuran.
- 31. The process of claim 27, wherein W is methyl or ethyl.
- 32. The process of claim 27, wherein R13 is selected from the group consisting of chloro, bromo and fluoro.
- 33. The process of claim 27, wherein R13 is bromo.
- 34. The process of claim 27, further comprising removal of the carboxy protecting groups W to form the homophthalic acid derivative of the formula:
- 35. The process of claim 34, further comprising dehydration of said homophthalic acid derivative to form the homophthalic anhydride of the formula:
- 36. The process of claim 35, further comprising preparation of isocoumarin derivatives of the formula:
- 37. The process of claim 36, wherein Y is an acyl activating group selected from the group consisting of halogen, imidazoyl, pyridyl and aryloxy.
- 38. The process of claim 37, wherein said halogen is chloro, bromo or iodo.
- 39. The process of claim 36, wherein Y is imidazoyl.
- 40. The process of claim 36, wherein said second solvent is an aprotic solvent.
- 41. The process of claim 40, wherein said aprotic solvent is a halogenated or ethereal solvent.
- 42. The process of claim 40, wherein said aprotic solvent is acetonitrile or N-methyl pyrrolidinone.
- 43. The process of claim 36, wherein said second base is selected from the group consisting of tertiary amine, amidine, amide and tertiary alkoxide bases.
- 44. The process of claim 36, wherein said second base if triethylanine.
- 45. The process of claim 36, wherein said second base is 1,8-diazabicylco[5.4.0]-undec-7-ene.
- 46. The process of claim 36, wherein R11 is methyl, R12 is ethyl, and R9 and R10 are methoxy and said isocoumarin derivative is:
- 47. The process of claim 46, further comprising removal of removal of the ethyl ester group and a methyl group from said isocoumarin derivative:
Parent Case Info
[0001] This application claims priority to U.S. application Ser. No. 60/303,532, filed Jul. 6, 2001 and to U.S. application Ser. No. 60/352,407, filed Jan. 28, 2002.
Provisional Applications (2)
|
Number |
Date |
Country |
|
60303532 |
Jul 2001 |
US |
|
60352407 |
Jan 2002 |
US |