N-Methylamino acids in peptide synthesis. V. The synthesis of N-tert-butyloxycarbonyl, N-methylamino acids by N-methylation

The preparation of enantiomerically pure N-tert-butyloxycarbonyl,N-methylamino acids by N-methylation of the parent amino acid derivatives using sodium hydride and methyl iodide in tetrahydrofuran at room temperature is described for neutral amino acids including O-benzyl-protected threonine and tyrosine. Methylation of the O-benzylserine derivative under these conditions gives the N-methyldehydroalanine derivative. The β-elimination is completely suppressed, giving the corresponding N-methylserine derivative when the reaction is carried out at 5 °C. Other related data on N-methylation and N-methylamino acid derivatives are presented.