Calcium(II)-mediated resolution of methyl o-chloromandelate with chiral O,O′-dibenzoyltartaric acid in preparative scale

• Published in: Main group metal chemistry Vol. 42; no. 1; pp. 19 - 22
• Main Authors: Xu, Hong-Wu, Wu, Li-Huan, Ren, Qiang, Liu, Cui-Yu, Yan, Guan-Qing
• Format: Journal Article
• Language: English
• Published: Berlin De Gruyter 02.04.2019; Walter de Gruyter GmbH
• Subjects: Acids; calcium(II); chloromandelate; coordination; dibenzoyltartaric acid; methyl; methyl (r)-o-chloromandelate; methyl (s)-o-chloromandelate; o,o′-dibenzoyltartaric acid; Reagents; resolution
• ISSN: 2191-0219; 0792-1241; 2191-0219
• DOI: 10.1515/mgmc-2018-0043

We report here the coordination-mediated resolution of methyl -chloromandelate, which is a key intermediate for clopidogrel, in preparative scale. The reaction of CaO, optically pure (2 , 3 )- ′-dibenzoyltartaric acid, and methyl -chloromandelate in ethanol solution afforded a mixed-ligands calcium(II) complex that was further purified by stirring of the crystals in hot methanol. Methyl ( )- -chloromandelate was obtained in good enantiomeric excess value (>99.5%) and yield (71%) by treatment of the complex with acid. At the same time, (2 , 3 )- ′-dibenzoyltartaric acid was recovered in 72% yield. In addition, methyl ( )- -chloromandelate was obtained in good enantiomeric excess value (>99.5%) and yield (73%) by recovery from the mother liquor and resolution with the same procedure for methyl ( )- -chloromandelate, except that (2 , 3 )- ′-dibenzoyltartaric acid was used as the resolving reagent.