A Simple and Robust Process for Large-Scale Synthesis of 4-Methylenepiperidine Hydrochloride

4-Methylenepiperidine hydrochloride 1 is a key intermediate for synthesis of the novel antifungal drug efinaconazole 2. In this work, a simple and robust process has been developed to synthesize 4-methylenepiperidine hydrochloride 1, with a high overall yield of 99.1% at a high purity of 99.7% in a large-scale. Moreover, this synthetic process avoided the uses of organolithium reagent and column chromatography process which are not desirable for industrial production.

Asymmetric bromine–lithium exchange: on the importance of both the diamine ligand and the organolithium reagent

The asymmetric bromine–lithium exchange on a series of prochiral biphenyls was investigated.