Synthesis of the stabilized active metabolite of clopidogrel

The convergent synthesis of the stabilized active metabolite of clopidogrel was achieved in eleven steps from commercially available 1,2,3,6-tetrahydropyridine and 2-bromo-3'-methoxy acetophenone (MPBr). This synthetic route used a standard Horner-Wadsworth-Emmons reaction allowing the introduction of a Z exocyclic double bond. A selective hydrolysis of an acrylic methyl ester moiety, isolated by an efficient and reliable preparative chiral chromatography at gram scale, released the title compound with a 98% LC purity and d.e. >99%. (C) 2014 Elsevier Ltd. All rights reserved.