Process development and scale-up of a β-secretase inhibitor via a stereospecific jocic reaction
A scalable process for the synthesis of a spiropiperidine β-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.
Henegar, Kevin E.,Lira, Ricardo,Kim, Hui,Gonzalez-Hernandez, Juan