Selective N-Monoalkylation of Amide Derivatives with Trialkyl Phosphates

A highly selective and easily handled monoalkylation of primary amide derivatives by using trialkyl phosphates as alkylating reagents in cyclopentyl methyl ether (CPME) was developed. Various monoalkylated amide derivatives were efficiently synthesized by changing the alkyl moiety (e.g., methyl, ethyl, butyl, or benzyl) of the trialkyl phosphate. These phosphate reagents are relatively stable and easily available, and CPME is a useful solvent in process chemistry.