N,N-Dialkoxycarbonylamino acid formation from a mixed anhydride through intramolecular urethane acylation

Methoxycarbonylation at the urethane nitrogen of N-benzyloxycarbonyl- and N-methoxycarbonylvaline has been identified as a side reaction accompanying the aminolysis of the mixed anhydride formed from the acid and methyl chloroformate when the anhydride is coupled in aqueous dimethylformamide and the nucleophile is an amino acid anion. The side reaction occurs to a lesser but still significant extent when the activated residue is leucyl.