Racemization of (S)-(+)-10,11-dimethoxyaporphine and (S)-(+)-aporphine: efficient preparations of (R)-(-)-apomorphine and (R)-(-)-aporphine via a recycle process of resolution

摘要

Efficient preparations of (R)-(-)-apomorphine (R)-1 and (R)-(-)-aporphine (R)-2 based on a recycle process of resolution are described. In this recycle process of resolution, (RS)-(+/-)- 10, 11 -dimethoxyaporphine 3 as the precursor of 1, and (RS)-()-aporphine 2 were successfully resolved into both enantiomers with (+)-dibenzoyltartaric acid (DBTA). The desired (R)-3 and (R)-2 were obtained and then, respectively, transformed to compound (R)-1, the hydrochloride salt of (R)-1, diacetate compound 4 and the hydrochloride salt of (R)-2; while the undesired (S)-3 and (S)-2 were racernized to obtain a racemate, which was suitable for further resolution. A method for the racemization of the undesired (S)-3 and (S)-2 was extensively studied, in order to obtain high-yielding racemization conditions. A plausible mechanism for the racemization of (S)-3 and (S)-2 was also proposed. (c) 2006 Elsevier Ltd. All rights reserved.