Synthetic Approaches to N-Methoxy-N-methylamides

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.