Direct Preparation of Amides from Amine Hydrochloride Salts and Orthoesters: A Synthetic and Mechanistic Perspective

<div><p></p><p>The 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 <i>O</i>-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.</p></div>