Patent ID: 7507843

Claim:
A process for stereoselective synthesis of a compound of Formula X wherein: R 1 is an aryl or heteroaryl group, each optionally independently substituted with one to three substituent groups, wherein each substituent group of R 1 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 hydroxy; and 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, the process comprising: (a) reacting the starting material of formula A where X is Cl, Br, or I, with magnesium metal in a suitable solvent to prepare a Grignard intermediate of formula B (b) reacting the Grignard intermediate of formula B with a disubstituted oxalate of formula C, where R 10 is an alkyl or aryl group, in a suitable solvent to obtain a compound of formula D (c) hydrolyzing the compound of formula D in a suitable solvent to obtain the carboxylic acid of formula E (d) coupling the carboxylic acid of formula E with R*ZH, where R*ZH is a chiral auxiliary and R* is a chiral residue and Z is O or NH, in a suitable solvent to obtain a compound of formula F (e) reacting the compound of formula F with trifluoromethide ion source YCF 3 in a suitable solvent to make the compound of formula G (f) hydrolyzing the compound of formula G to remove the chiral auxiliary group R*ZH and obtain the compound of formula H (g) reducing the compound of formula H to obtain the compound of formula I (h) cyclizing the compound of formula I to obtain the epoxide compound of formula X