An unconventional method for purifying the N-carboxyanhydride derivatives of γ-alkyl-L-glutamates

Common impurities in the phosgenation of alpha-amino acids to produce their N-carboxyanhydride (NCA) derivatives include hydrogen chloride and the hydrochloride salt of the starting amino acid. These impurities can be effectively removed by washing the reaction mixture with water and aqueous bicarbonate at 0 degrees C prior to isolation of the NCA., despite the well known sensitivity of the NCA to water. The method should be particularly useful for NCA derivatives which are isolated as oils since purifying them by recrystallization or solvent washes is not feasible. This study involved specifically the purification of NCA derivatives from a variety of gamma-alkyl-L-glutamates and gamma-benzyl-L-glutamate.