A fast and simple one-pot synthesis of carbamoyl azides of α-N-protected amino acids is reported. The procedure involves the reaction between sodium azide and the mixed anhydride obtained from an α-N-protected amino acid and isobutyl chloroformate, in the presence of KH2PO4. The reaction rate was influenced by the nature of both the α-N-protection and the amino acid side chain. Surprisingly, tert-butyloxycarbonyl (α-N-Boc) and benzyloxycarbonyl (α-N-Cbz) protected proline afforded the corresponding isocyanates instead of the expected carbamoyl azides.
α-N-protected amino acids - sodium azide - carbamoyl azide - mixed anhydride - Curtius rearrangement
