lsyc_a_1096943_sm8269.pdf (1.57 MB)
Direct Preparation of Amides from Amine Hydrochloride Salts and Orthoesters: A Synthetic and Mechanistic Perspective
Version 2 2015-11-18, 20:43
Version 1 2015-11-17, 00:00
journal contribution
posted on 2015-11-18, 20:43 authored by Martin J. Di Grandi, Caitlin Bennett, Kristen Cagino, Arnold Muccini, Corey Suraci, Shahrokh SabaThe conversion of a wide range of primary and secondary aliphatic and a few arylamine hydrochloride salts to their corresponding acetamides with trimethyl orthoacetate is described. Mechanistic studies using NMR and gas chromatography–mass spectrometry techniques indicate these reactions proceed via an O-methylimidate intermediate that undergoes in situ demethylation by chloride, affording the corresponding acetamides. Synthetically, this reaction represents a practical, high-yielding protocol with a simple workup for the rapid conversion of amine hydrochloride salts to acetamides.