Synthesis of N-alkyl- N-methyl amino acids. Scope and limitations of base-induced N-alkylation of Cbz-amino acids

Abstract

The reaction of N-benzyloxycarbonyl derivatives of aliphatic amino acids with NaH/alkyl iodides gave the corresponding N-Cbz- N-alkyl derivatives in good to high yields. The scope and limitations of this simple N-alkylation reaction were investigated as a convenient and flexible attempt to prepare unsymmetrically N,N-diprotected α-amino acids. The procedure is based on the N-alkylation of N-carbamoyl amino acids, a one-pot deprotection/protection sequence without extensive purification of the products. Protection of the carboxyl function is not required while the starting materials are inexpensive and commercially available.