Synthetic Approaches to N‐Methoxy‐N‐methylamides

Abstract

N‐Methoxy‐N‐methylamides were prepared by the acylation of acid halides, acyl cyanides, esters, lactones, activated amides, and mesyl carboxylates with N,O‐dimethylhydroxylamine hydrochloride. The reaction of carboxylic acids with alkyl chloroformates, phosphonate reagents, or coupling agents afforded the activated esters, which were converted to N‐methoxy‐N‐methylamides by (CH3O)NHCH3. N‐Methoxy‐N‐methylamides were also prepared by the oxidative amidation of benzyl alcohols and palladium‐catalyzed aminocarbonylation of organoboronic acids or aryl halides with (CH3O)NHCH3 under CO equivalents. Furthermore, N‐methoxy‐N‐methylamides were produced by the selective substitution of N,O‐dimethylcarbamoylation agents with organometallic reagents.