Claims
- 1. A process for the preparation of a compound of the formula
- 2. The process of claim 1, wherein the chlorinating agent is RaSO2Cl.
- 3. The process of claim 2, wherein the chlorinating agent is methanesulfonyl chloride.
- 4. The process of claim 1, wherein the chlorinating is conducted in a polar or dipolar aprotic solvent.
- 5. The process of claim 3, wherein there is from about 2 to 3 equivalents of methanesulfonyl chloride.
- 6. The process of claim 1, wherein a concentration of the compound 2 is from about 1 to 2 M.
- 7. The process of claim 1, wherein the reaction is performed at a temperature of from about 45 to 90° C.
- 8. The process of claim 1, wherein R1 and R3 are H;
R4 is H, halogen or cyano; and R6 is H, methyl or allyl.
- 9. The process of claim 8, wherein R4 and R6 are H.
- 10. A process for the preparation of a compound of the formula
- 11. The process of claim 10, wherein R7 is CH3.
- 12. The process of claim 10, wherein
R1 is H, or C1-C3 alkyl; R3 is H; R4 is H, halogen, cyano or C(O)R5; and R6 is H, C1-C3 alkyl, allyl or benzyl.
- 13. The process of claim 12, wherein R3 and R4 are H, and R6 is H.
- 14. The process of claim 10, wherein the treatment with potassium alkoxide is accomplished by heating in a suspension of a carbocyclic aromatic solvent and diatomaceous earth at a temperature of about 105 to about 120° C.
- 15. The process of claim 14, wherein the potassium alkoxide is potassium methoxide.
- 16. The process of claim 15, wherein there is at least 2 equivalents of potassium methoxide relative to the compound of formula 3.
- 17. The process of claim 14, wherein the carbocyclic aromatic solvent is toluene.
- 18. The process of claim 17, wherein there is from about 15 to 40 mL of toluene and from about 1 to 2 g of diatomaceous earth per gram of the compound of the formula 3.
- 19. The process of claim 10, further comprising simultaneous treatment with a lithium alkoxide of the formula
- 20. The process of claim 19, wherein the carbocyclic aromatic solvent is xylene.
- 21. The process of claim 19, wherein there is from about 0.8 to about 1 M of the compound of the formula 3.
- 22. The process of claim 19, wherein the alkoxides are potassium methoxide and lithium methoxide.
- 23. The process of claim 22, wherein there is from about 2 to 5 equivalents of potassium methoxide and from about 1 to 2 equivalents of lithium methoxide.
- 24. The process of claim 22, wherein a temperature of about 110 to 125° C. is maintained during the treatment with potassium methoxide.
- 25. A process for the preparation of a compound of the formula
- 26. The process of claim 25, wherein the Lewis acid is aluminum trichloride present in an amount of at least four equivalents.
- 27. The process of claim 25, wherein the reaction is conducted in a solvent of dichloromethane: [C1-C3]nitroalkane in about a 4:1 to 17:3 ratio.
- 28. A process for the preparation of a compound of the formula
- 29. The process of claim 28, wherein the chlorination of step (a) comprises treatment with about 2 to 3 equivalents of methanesulfonyl in a polar aprotic solvent at a temperature of about 45 to 90° C.
- 30. The process of claim 28, wherein the Lewis acid in step (c) is aluminum trichloride.
- 31. The process of claim 28, wherein in step (c), the compound of the formula 9 is methyl chlorooxoacetate.
- 32. The process of claim 28, wherein the acyl activating agent in step (e) is selected from the group consisting of Vilsmeier reagent and oxalyl chloride.
- 33. The process of claim 28, wherein the coupling of step (e) comprises:
(i) treating the compound of the formula 6 with Vilsmeier reagent; and (ii) treating the product from step (i) with the compound of the formula 8.
- 34. The process of claim 28, wherein the compound of the formula 2 is prepared by a process comprising: oxidizing a compound of the formula
- 35. The process of the claim 34, wherein the oxidizing agent in the oxidation of step (a) is selected from the group consisting of m-chloroperoxybenzoic acid, hydrogen peroxide, peracetic acid, hydrogen peroxide-urea reagent, magnesium monoperoxyphthalate hexahydrate, and oxone.
- 36. The process of claim 35, wherein the oxidizing agent is m-chloroperoxybenzoic acid.
- 37. The process of claim 36, wherein the oxidation of step (a) comprises treatment with from about 1 to 3 equivalents of meta-chloroperoxybenzoic acid in ethyl acetate.
- 38. The process of claim 28, wherein R7 is CH3O.
- 39. The process of claim 38, wherein R1, R3, R4 and R6 are H.
- 40. The process of claim 39, wherein the compound of formula 8 in step (e) is
- 41. A compound of the formula:
- 42. A compound of the formula:
Parent Case Info
[0001] This application claims a benefit of priority from U.S. Provisional Application No. 60/367,401, the entire disclosure of which is herein incorporated by reference.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60367401 |
Mar 2002 |
US |