Claims
- 1. A method for preparing compounds having Formula (S1), (S2), or (S3) as follows:
- 2. The method according to claim 1, wherein the molar ratio of a disilyloxydiene of Formula (II) to an aldehyde of Formula (Q1), (Q2), or (Q3) initially present in the reaction mixture ranges from 1:1 to 6:1.
- 3. The method according to claim 1, wherein the disilyloxydiene of Formula (II) is prepared by
(a) reacting an acetoacetate of the Formula (VI) 26 with a silylating agent in the presence of a base and an organic solvent to form a silylenolether having Formula (VII) 27and (b) treating the silylenolether having Formula (VII) with a base and a silylating agent in an inert solvent to form the disilyloxydiene of Formula (II), wherein
R1 is, independently, an unsubstituted or substituted alkyl, cycloalkyl or aralkyl; and R is a lower alkyl.
- 4. The method according to claim 3, wherein the organic solvent in step (a) is hexane, and the inert solvent in step (b) is diethylether or tetrahydrofuran.
- 5. The method according to claim 3, wherein the base in step (a) is triethylamine.
- 6. The method according to claim 3, wherein the base in step (b) is selected from the group consisting of lithium diisopropylamide, lithium bis(trimethylsilyl)amide, sodium bis(trimethylsilyl)amide, and potassium bis(trimethylsilyl)amide.
- 7. The method according to claim 3, wherein the silylating agent is trimethylsilyl chloride or triethylsilyl chloride.
- 8. The method according to claim 1 wherein the titanium (IV) catalyst of Formula (IV) is prepared in situ by reacting titanium (IV) tetraisopropoxide with (S)-2,2′-binaphthol of the Formula (VIII)
- 9. The method according to claim 8, wherein the molar ratio of the titanium (IV) catalyst of Formula (IV) to an aldehyde of Formula (II) initially present in the reaction mixture ranges from 0.01:1 to 0.15:1.
- 10. The method according to claim 1, wherein R1 is lower alkyl, R2 is halogen; and R3, R4, R5, R6 and R7 are hydrogen.
- 11. The method according to claim 10, wherein R1 is ethyl; and R2 is fluorine.
- 12. A method for preparing syn-3(R),5(S)-dihydroxyesters having Formula (V1), (V2), or (V3) as follows:
- 13. The method according to claim 12, wherein the di(lower alkyl)methoxyborane is diethylmethoxyborane or dibutyl-methoxyborane.
- 14. The method according to claim 12, wherein the polar solvent is selected from the group consisting of tetrahydrofuran, methanol, ethanol, isopropanol, butanol, and mixtures thereof.
- 15. The method according to claim 12, wherein the reducing agent is sodium borohydride or lithium borohydride.
- 16. A method for preparing calcium salts having Formula (W1), (W2), or (W3) as follows:
- 17. The method according to claim 16, wherein the calcium source in step (d) is calcium chloride.
- 18. A method for preparing calcium salts having Formula (W1), (W2), or (W3) as follows:
- 19. The method according to claim 18, wherein the acid in step (c) is concentrated hydrochloric acid, the aprotic water-miscible solvent is acetonitrile, and the acid addition salt thereof is the hydrochloric acid salt.
- 20. A method for preparing an alkali metal salt having Formula (X1), (X2), or (X3) as follows:
- 21. The method according to claim 20, wherein the aqueous base in step (c) is sodium hydroxide and M represents sodium.
- 22. The method according to claim 20 which additionally comprises a molecular sieve in step (a).
- 23. The method according to claim 22, wherein water is added to the molecular sieve prior to using the molecular sieve in step (a).
- 24. The method according to claim 23, wherein the water content of the molecular sieve is from about 1 wt % to about 15 wt %, based on the total weight of the titanium (IV) catalyst.
- 25. The method according to claim 24, wherein the water content of the molecular sieve is from about 2.6 wt % to about 10 wt %.
- 26. The method according to claim 22 wherein the molecular sieve is situated in a fixed bed external to a reaction vessel in which step (a) is conducted, and the reaction mixture in step (a) is passed through the fixed bed.
- 27. The method according to claim 26 wherein the molecular sieve is reused.
Parent Case Info
[0001] This application claims the benefit of U.S. Provisional Application No. 60/352,316, filed Jan. 28, 2002, and U.S. Provisional Application No. 60/383,188, filed May 24, 2002 which in their entirety are herein incorporated by reference.
Provisional Applications (2)
|
Number |
Date |
Country |
|
60352316 |
Jan 2002 |
US |
|
60383188 |
May 2002 |
US |