Development of a Safe and Efficient Two-Step Synthesis for Preparing 1-Bromoacetyl-3,3-dinitroazetidine, a Novel Clinical Anticancer Candidate

An efficient process for synthesizing and isolating a new investigative anticancer agent, 1-bromoacetyl-3,3-dinitroazetidine, is described. The reaction entails a sequence of oxidative nitration followed by acylative dealkylation. The methods reported give 50-60-g batches of high-purity product without a designated purification step. The reaction conditions have been designed to mitigate the safety concerns associated with gem-dinitroazetidines. Some observations on the acylative dealkylation mechanism are discussed.