Synthesis of N-Methylamino Acid Derivatives from Amino Acid Derivatives using Sodium Hydride/Methyl Iodide

Abstract

Reaction of N-acetyl-, N-benzoyl-, and N-carbobenzoxy derivatives of aliphatic amino acids with sodium hydride/methyl iodide in tetrahydrofuran containing dimethylformamide at 80° gave the corresponding N-methylamino acid methyl esters as oils in high yields. Saponification of these gave the N-protected-N-methylamino acids, and decarbobenzoxylation gave the N-methylamino acid methyl ester hydrobomides. The products are essentially optically pure and free of unmethylated amino acid derivative.