Asymmetric reduction process

摘要

The present invention relates to a stereoselective reduction procedure to obtain, by means of catalytic asymmetric hydrogenation by hydrogen transfer, a compound of formula (I) in which X is S or SO2 and R4 is hydrogen or an SO2NH2 group, from the corresponding ketone precursor, said compound of formula (I) being useful as an intermediate in the preparation of dorzolamide or of the hydrochloride salt thereof.;

主权项

1. A reduction process to obtain, stereoselectively, a compound of formula (I) wherein X is S or SO2 and R4 is hydrogen or SO2NH2;said process comprising asymmetric catalytic hydrogenating by hydrogen transfer a compound of formula (II), wherein X and R4 areas defined above, using formic acid, a salt thereof, said salt being sodium, ammonium or triethylammonium formate, or a C1-C3 alcohol as a hydrogen source, working in the presence of a base and of a catalyst of formula (III) or (IV), wherein the dashed, curved line represents an optional single bond which exists when n is not zero; R is SO2C6H4-p-CH3, SO2CH3 or SO2C6F5; R1 is absent, 1-CH3-4-CH(CH3)2, 1,3,5-(CH3)3 or 1,3,4,5,6-(CH3)6; R2 and R3 are both an unsubstituted phenyl group or R2 and R3, taken together, are a —(CH2)4— group; n is a number from zero to 3; and M is rhodium (Rh) or iridium (Ir) and wherein the compound of formula (I), is obtained with a yield of at least 90% compared to the diastereoisomer cis-(4R,6S).