Patent ID: 7026143

Claim:
A method of stereoselectively producing a desired enantiomer of a compound of formula I: wherein Ar is C 6 or C 10 aromatic group that can be substituted with H, C 1 to C 6 alkyl, trifluoromethyl or halo, R 1 is H or acetyl, and R 2 is H or C 1 to C 6 alkyl, the method comprising: reacting Ar—CH 2 —X, where X is a leaving group, with R 4 —C(O)—CH 2 —C(O)O—R 2* , wherein R 2* and R 4 are independently C 1 to C 6 alkyl; reacting a resulting compound of formula II: with a halogenating agent which comprises an N-halo substituted amide, N-halosubstituted imide, N-halosubstituted thioamide, or N-halosubstituted thioimide as the halogenating moiety to produce, with or without an additional hydrolysis of the ester, a compound of formula III: wherein Y is the leaving group; reacting the compound of formula III with Z—S—R 1 *, wherein R 1 * is acetyl, and Z is K, Na, or other cation to produce a compound of formula I*: and conducting one of the following stereoselective reactions: (a) (1) reacting the compound of formula III with a hydrolase that is stereoselective for the ester; (2) isolating the desired resulting acid; (3) racemizing residual compound of formula III; and (4) conducting at least one additional iteration of steps (a)(1) and (a)(2) with the racemized residual compound of formula III, wherein the reacting with Z—S—R 1 * is conducted with stereoselective inversion of the chiral carbon; or (b) (1) reacting the compound of formula I* with a hydrolase that is stereoselective for the ester; (2) isolating the desired resulting acid; (3) racemizing residual compound of formula I*; and (4) conducting at least one additional iteration of steps b(1) and b(2) with the residual racemized compound of formula I*.