A Convenient Method for the Conversion of Hindered Carboxylic Acids to <i>N</i>-Methoxy-<i>N</i>-methyl (Weinreb) Amides

Abstract

The conversion of sterically hindered carboxylic acids to N-methoxy-N-methyl amides can be efficiently carried out with 1.1 equiv of methanesulfonyl chloride, 3 equiv of triethylamine, and 1.1 equiv of N-methoxy-N-methylamine. Yields for this process range from 59% to 88%. The major byproduct in these reactions, N-methoxy-N-methylmethanesulfonamide, can be removed by placing the product mixture under vacuum for 14-24 h.