L-Aspartic Acid → N-(1-methylcyclobutyloxycarbonyl) aspartic acid dimethyl ester

Participants

Reaction Steps

An example of the use of the novel N-protected-α-amino acid compounds of this invention in peptide synthesis is the preparation of α-aspartyl-phenylalanine methyl ester, a known sweetening agent. The dipeptide is conveniently prepared by coupling N-(1-methylcyclobutyloxycarbonyl) aspartic anhydride with phenylalanine methyl ester hydrochloride. Introduction of the N-(1-methylcyclobutyloxycarbonyl blocking group into aspartic acid is accomplished by reacting 1-methylcyclobutylchloroformate with aspartic acid dimethyl ester in accordance with the process of this invention. Equimolar quantities of the chloroformate and aspartic acid dimethyl ester are reacted in chloroform at 0°C. at pH 8. Reaction is carried out by portion-wise addition of 1-methylcyclobutyl chloroformate to the aspartic acid suspended in chloroform. Triethylamine is added to the reaction during the addition to maintain pH 8. After allowing the reaction to run to completion at room temperature, the reaction mixture is treated according to the procedure outlined above to afford the N-(1-methylcyclobutyloxycarbonyl) aspartic acid dimethyl ester. The free acid is obtained by saponifying the ester in a basic aqueous methanol solution. After acidifying the reaction mixture with sulfuric acid, the N-(1-methylcyclobutyloxycarbonyl) aspartic acid is isolated by extraction.

Provenance & Evidence