Patent ID: 6207822
Filing Date: 2001-03-27
Classification: C07D,Y02P

Abstract:
A process for preparing a compound represented by the formula ##STR22##comprising:(a) reacting p-fluorobenzoylbutyric acid of formula II with pivaloyl chloride and acylating the product with a chiral auxiliary of formula III to obtain a ketone of formula IV: ##STR23##wherein X is --O--, --S-- or --N(C.sub.1 -C.sub.6 alkyl); Y is .dbd.O or .dbd.S; and R.sup.1 is C.sub.1 -C.sub.6 alkyl, phenyl, naphthyl, substituted phenyl, substituted naphthyl, C.sub.1 -C.sub.6 alkoxycarbonyl or benzyl, wherein the substituents on phenyl and naphthyl are 1-3 substituents selected from the group consisting of C.sub.1 -C.sub.6 alkyl, phenyl and benzyl;(b) reducing the ketone of formula IV in the presence of a chiral catalyst to an alcohol of formula V: ##STR24##(c) reacting the chiral alcohol of formula V, an imine of formula VI and a hydroxy protecting agent, then condensing the hydroxy-protected compounds to obtain a .beta.-(substituted-amino)amide of formula VII, wherein Prot is a hydroxy protecting group: ##STR25##(d) cyclizing the .beta.-(substituted-amino)amide of formula VII with(i) a silylating agent and a fluoride ion catalyst cyclizing agent;(ii) a silylating agent and a quaternary ammonium salt of a chiral auxiliary of formula III; or(iii) a strong non-nucleophlic base;to obtain the compound of formula VIII: ##STR26##(e) removing the hydroxy protecting groups.