Patent ID: 7928241

Claim:
A process for the stereoselective synthesis of a benzimidazole sulfoxide of formula I or a salt thereof either as a single enantiomer or in an enantiomerically enriched form: wherein R is X is and R 1 -R 4 are the same or different and selected from hydrogen, alkyl, alkoxy, halogen, halo-alkoxy, alkylcarbonyl, alkoxycarbonyl, oxazolyl, trifluroalkyl, or adjacent groups R 1 -R 4 form ring structures which may be further substituted; wherein R 5 and R 7 are same or different and selected from hydrogen, alkyl, alkylthio, alkoxy optionally substituted by fluorine, alkoxyalkoxy, dialkylamino, piperidino, morpholino, halogen, phenylalkyl and phenylalkoxy; R 6 is selected from hydrogen, alkyl, alkylthio, alkoxy optionally substituted by fluorine, alkoxyalkoxy, dialkylamino, piperidino, morpholino, halogen, nitro, phenylalkyl and phenylalkoxy; R 8 is hydrogen or forms an alkylene chain together with R 7 and R 9 and R 10 are, same or different and selected from hydrogen, halogen and alkyl; which comprises: a) reacting a benzimidazole sulfide of formula II, or a salt thereof: wherein R, X and R 1 -R 4 are as defined for formula I; with a chiral compound of formula III: R c —Z—Y III wherein R c is a chiral moiety having at least one asymmetric center and at least one asymmetric center in the chiral moiety can have either R or S configuration; Z is: and Y is a leaving group to provide a compound of formula IV: wherein R, X and R 1 -R 4 are as defined for formula I; and R c and Z are as defined for formula III; b) oxidizing the compound of formula IV to give a diastereomeric excess of compound of formula V: wherein R, X, R c , R1-R4 and Z are as defined for formula IV and star (*) refers to excess of one configuration at the sulfur atom of the sulfoxide group over the opposite configuration; c) if required, separating the diastereomers of formula V; and d) deprotecting the product of step (b); or separated diastereomers of step (c) with an acid or base to provide a single enantiomer or enantiomerically enriched compound of formula I and optionally preparing the enantiomer formed as the salt.