Patent ID: 7179919

Claim:
A process for stereoselective synthesis of a compound of formula (G) wherein: R′ is an aryl or heteroaryl group, each optionally independently substituted with one to three substituent groups, wherein each substituent group of R1 is independently C 1 –C 5 alkyl, C 2 –C 5 alkenyl, C 2 –C 5 alkynyl, C 3 –C 8 cycloalkyl, heterocyclyl, aryl, heteroaryl, C 1 –C 5 alkoxy, C 2 –C 5 alkenyloxy, C 2 –C 5 alkynyloxy, aryloxy, C 1 –C 5 alkanoyloxy, C 1 –C 5 alkanoyl, aroyl, trifluoromethyl, trifluoromethoxy, or C 1 –C 5 alkylthio, wherein each substituent group of R 1 is optionally independently substituted with one to three substituent groups selected from methyl, methoxy, fluoro, chloro, or alkoxy; R 2 and R 3 are each independently hydrogen or C 1 –C 5 alkyl, or R 2 and R 3 together with the carbon atom they are commonly attached to form a C 3 –C 8 spiro cycloalkyl ring; R 4 is C 1 –C 5 alkyl, C 2 –C 5 alkenyl, or C 2 –C 5 alkynyl, each optionally independently substituted with one to three substituent groups, wherein each substituent group of R 4 is independently C 1 –C 3 alkyl, hydroxy, halogen, amino, or oxo; and R 5 is a heteroaryl group optionally independently substituted with one to three substituent groups, wherein each substituent group of R 5 is independently C 1 –C 5 alkyl, C 3 –C 8 cycloalkyl, C 1 –C 5 alkoxy trifluoromethyl, trifluoromethoxy, trifluoromethylthio, or C 1–C 5 alkylthio, wherein each substituent group of R 5 is optionally independently substituted with one to three substituent groups selected from C 1 –C 3 alkyl, C 1 –C 3 alkoxy, or trifluoromethyl, the process comprising: (a) reacting a starting material of formula A with a first protecting group agent PG-Y, where Y is a leaving group, in a suitable solvent, followed by addition of an acetylating reagent and a suitable base to prepare a protected intermediate of formula B (b) reacting the protected intermediate of formula B with a trifluoromethyl-substituted ketone of formula C in the presence of a suitable base in a suitable solvent to obtain a compound of formula D (c) reacting the compound of formula D with a suitable metal alkoxide, (R A —O),μM, where R A is an alkyl or aryl group, M is a suitable metal atom, and μ is an integer number, in a suitable solvent followed by reaction of the tertiary alcohol with a second protecting group agent PG′-Y′, where Y′ is a leaving group, to obtain the ester of formula E (c′) hydrolyzing the compound of formula D followed by esterification of the free acid with a suitable alcohol, R B —OH, where R B is an alkyl or aryl group, and protection of the tertiary alcohol as in (c) to provide the ester of formula E (d) reacting the ester of formula E with the compound of formula F, where one or two of W, X, Y, or Z is N and the remaining are CH optionally substituted on the ring or methyl group with a substituent compatible with alkyl lithium, in the presence of a suitable base, in a suitable solvent to obtain a compound of formula G