Claims
- 1. A process for the preparation of a compound of formula (I)
- 2. The process of claim 1 wherein the compound of Formula 1 is optically active.
- 3. The process of claim 2 wherein the compound of Formula 1 has an enantiomeric excess of greater than about 80%.
- 4. The process of claim 3 wherein the compound of Formula 1 has a high level of enantiomeric purity.
- 5. The process of claim 4, wherein R1 is selected from H, C16 alkyl substituted with 0-3 R3, a C6-10 aryl substituted with 0-3 R3, wherein the aryl is selected from phenyl and naphthyl, and a a 5-6 membered heterocycle having 1-2 heteroatoms selected from O, N, and S, the heterocycle being substituted with 0-3 R3, they heterocycle being selected from 2-furanyl, 3-furanyl, 2-thienyl, 3-thienyl, oxetanyl, tetrahydrofuranyl, or pyranyl;
R3 is selected from C1-4 alkyl, CF3, F, Cl, Br, I, CN, NO2, —O—R4, —C(O)OR4a, —NHC(O)R4, —C(O)NHR4, —OC(O)R4, and phenyl substituted with 0-3 R5.
- 6. The process of claim 5, wherein
R1 is selected from H, C16 alkyl selected from methyl, ethyl, propyl, i-propyl, butyl, i-butyl, sec-butyl, t-butyl, and pentyl, phenyl substituted with 0-2 R3, furanyl substituted with 0-1 R3; and R3 is selected from C1-4 alkyl, CF3, F, Cl, Br, and I.
- 7. The process of claim 6 wherein
L is selected from 1,5-cyclooctadiene and norbornadiene; and X is selected from BF4−, PF6−, SbF6−, ClO4−, AsF6−, O3SCF3−, O2CCF3−, and B(C6F6)4−.
- 8. The process of claim 7 wherein the catalyst is generated in the reaction mixture by sequential addition of an iridium complex of Formula L2Ir+X− and 1.0 to 1.1 molar equivalents of (R,R)-3 or (S,S)-3.
- 9. The process of claim 8 wherein n is selected from 1 and 2.
- 10. The process of claim 9 wherein R1 is selected from the group consisting of phenyl, p-fluorophenyl, p-methoxyphenyl, p-trifluormethylphenyl, 2-furanyl, or n-propyl.
- 11. The process of claim 10 wherein the process further comprises filtering the resultant solution through a bed of solid scavenger to remove catalyst residues.
- 12. The process of claim 11 wherein the process further comprises removal of the reaction solvent by distillation, and crystallizing the product of Formula I to achieve a high level of enantiomeric purity.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the priority benefit of U.S. Provisional Application No. 60/365,612, filed Mar. 19, 2002, the disclosure of which is incorporated herein by reference in its entirety.
Provisional Applications (1)
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Number |
Date |
Country |
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60365612 |
Mar 2002 |
US |