An improved method for the N-tert-butoxycarbonyl protection of the amino functionality of alpha-alkylated prolines and other sterically hindered alpha,alpha-disubstituted amino acids has been developed in which the lipophilic base tetramethylammonium hydroxide is used to solubilize the otherwise insoluble zwitterionic amino acid in acetonitrile, thereby obviating the need for an aqueous medium. Copyright (C) 1996 Elsevier Science Ltd