Process Development and Scale-up of a beta-Secretase Inhibitor via a Stereospecific Jocic Reaction

A scalable process for the synthesis of a spiropiperidine beta-secretase inhibitor is described. Key stereochemical transformations utilized are a diastereoselective trichloromethyl addition followed by an unprecedented stereospecific Jocic reaction with an aniline nucleophile. Simplified processing was developed for a Dieckmann cyclization/decarboxylation sequence to give a process suitable for the production of kilogram quantities of API.