Synthesis of N-Substituted piperidines from piperidone

Abstract

A reductive amination reaction between N-boc-piperidin-4-one and 3,4-dichloroaniline was successfully employed for the synthesis of the N-(3,4-dichloropheny)-N-(2-phenoxylethyl) piperidin-4-amine. The synthesis of a small set of derivatives of this promising scaffold modified on the piperidine nitrogen is also reported. Three-carbon modified derivatives were synthesized using a simple aza-Michael reaction with acrylonitrile and tert-butyl acrylate, whereas two-carbon elongation products were obtained by alkylation with bromoacetonitrile, 2-iodoethanol and 2- chloro-N, N-dimethylethylamines.