Enantioselective Synthesis of ((1 R ,2 R )-Cyclohexane-1,2-diyl)bis(methylene)dimethanesulfonate, a Lurasidone Hydrochloride Intermediate.

A concise, economical, and highly enantioselective synthesis of bismesylate intermediate of lurasidone HCl, an antipsychotic, has been developed. The key steps involved in the synthesis are thionyl chloride–catalyzed esterification of tetrahydrophthalic anhydride in MeOH, epimerization ofcistotransisomer, hydrolysis of the diester, resolution of the diacid, reduction with Red-Al, and finally bismesylation of the corresponding diol, which provided the desired intermediate ((1 R,2 R)-cyclohexane-1,2-diyl)bis(methylene) dimethanesulfonate in overall good yield. [ABSTRACT FROM PUBLISHER]