Claims
- 1. A process for the preparation of an enantiomerically enriched mixture of a major and minor diatereoisomer compounds of structural formula I: wherein R1 is C1-4 alkyl; which comprises forming a salt of a compound of formula I with an (R)- or (S)-amino acid of structural formula II: wherein R2 is selected from the group consisting of phenyl, benzyl, 1-naphthylmethyl, 2-naphthylmethyl, 4-imidazolylmethyl, and 4-hydroxybenzyl; and and R3 is tert-butyl, benzyl or 9-fluorenylmethyl.
- 2. A process for the preparation of an enantiomerically enriched mixture of a major and minor diastereoisomer compounds of structural formula I: whereinR1 is C1-4 alkyl; comprising the steps of: (a) mixing a compound of structural formula I with an (R)- or (S)-amino acid of structural formula II: wherein R2 is selected from the group consisting of phenyl, benzyl, 1-naphthylmethyl, 2-naphthylmethyl, 4-imidazolylmethyl, and 4-hydroxybenzyl; and and R3 is tert-butyl, benzyl or 9-fluorenylmethyl; in an alcohol solvent system to form a mixture; (b) heating the mixture from about 10° C. to about 100° C.; (c) allowing the mixture to cool so that a crystalline (R)- or (S)-amino acid salt of said compound of formula I is formed; (d) filtering the mixture to separate the crystalline salt from the supernatant; and (e) liberating said compound of formula I from the crystalline salt by treating the salt with a base.
- 3. The process of claim 1 wherein R1 is methyl, ethyl, or tert-butyl.
- 4. The process of claim 1 wherein R2 is benzyl.
- 5. The process of claim 1 wherein R3 is benzyl.
- 6. The process of claim 1 wherein R2 and R3 are benzyl.
- 7. The process of claim 1 wherein the amino acid of structural formula II is N-(benzyloxycarbonyl)-(S)-phenylalanine.
- 8. The process of claim 2 wherein said alcohol solvent system is aqueous ethanol or aqueous methanol.
CROSS-REFERENCE TO RELATED APPLICATIONS
The present invention is related to U.S. provisional application Serial No. 60/306,502, filed Jul. 19, 2001, the contents of which are hereby incorporated by reference in their entirety.
US Referenced Citations (1)
Number |
Name |
Date |
Kind |
6017926 |
Askew et al. |
Jan 2000 |
A |
Foreign Referenced Citations (1)
Number |
Date |
Country |
WO 0134602 |
May 2001 |
WO |
Non-Patent Literature Citations (3)
Entry |
S.G. Davies et al., Tetrahedron: Asymmetry, vol. 2, No. 3, pp. 183-186 (1991).* |
S. G. Davies et al., Tetrahedron: Asymmetry vol. 2, No.3, pp.183-186 (1991). |
H. Marlon Zhong et al., Tetrahedron Letters 40 pp. 7721-7725 (1999). |
Provisional Applications (1)
|
Number |
Date |
Country |
|
60/306502 |
Jul 2001 |
US |