Patent ID: 7285670

Claim:
A method of preparing an alkylated thiazoline carboxylic acid or a derivative thereof represented by Structural Formula (I): or a salt thereof, wherein R 1 is a substituted or unsubstituted alkyl group; each R 2 is, independently, —H or a substituted or unsubstituted alkyl group; R 3 is —H, a substituted or unsubstituted alkyl group or a carboxyl protecting group; and n is an integer from 1 to 5, the method comprising: (a) coupling a compound represented by Structural Formula (II): wherein each R 4 is, independently, a substituted or unsubstituted alkyl group and n is an integer from 1 to 5, with a cysteine ester represented by Structural Formula (III): wherein A is an anion and R 5 is a substituted or unsubstituted alkyl group, thereby forming a substituted thiazoline carboxylic acid ester represented by Structural Formula (IV): (b) optionally, hydrolyzing the substituted thiazoline carboxylic acid ester to form a substituted thiazoline carboxylic acid represented by Structural Formula (V): (c) optionally, protecting the carboxyl group of the substituted thiazoline carboxylic acid to form a protected thiazoline carboxylic acid represented by Structural Formula (VI): wherein R 6 is a carboxyl protecting group; (d) alkylating the optionally protected thiazoline carboxylic acid represented by Structural Formula (VII): wherein R 4 and n are as defined above and R 7 is —H, R 5 or R 6 , with a compound having the formula R 1 -L, wherein R 1 is defined as above and L is a leaving group, in the presence of a chiral phase transfer catalyst to produce an enantiomeric excess of either the (R)- or (S)-isomer of an alkylated optionally protected thiazoline carboxylic acid represented by Structural Formula (VIII): (e) optionally, hydrolyzing the optionally protected alkylated thiazoline carboxylic acid and cleaving ether groups, thereby forming the compound represented by Structural Formula (I).