Fremgangsmåde til syntese af (2S,3aS,7aS)-perhydroindol-2-carboxylsyre og estere heraf og anvendelse heraf ved syntese af perindopril

摘要

Preparation of (2S, 3aS, 7aS)-perhydroindole-2-carboxylic acid (I) and its esters. Preparation of (2S, 3aS, 7aS)-perhydroindole-2-carboxylic acid (I) and its esters by condensation of a protected (L)-serine (III) with an aromatic ketone (IV) to form (V), which undergoes diastereoselective reduction to form (VI). This is then condensed with cyclohexanone to form (VII), halogenated to form (VIII), and is cyclized in the presence of a radical initiator and tributyl tin hydride to form (IX). Removal of the amine protecting group, and optionally the esterifying group, gives (I). R = H, benzyl or 1-6C alkyl R1 = 1-6C alkyl, or benzyl; Ar = phenyl optionally substituted by one or more 1-6C alkyl groups, or naphthyl; and X = Cl, Br, or I. Independent claims are included for the following: (1) intermediates of formula (VII) and (VIII); and (2) Preparing perindopril using (I) prepared by the new process.