A ONE-POT PROCESS FOR THE PREPARATION OF ALPHA-L-ASPARTYL-L-PHENYLALANINE METHYL ESTER HYDROCHLORIDE AND ALPHA-L-ASPARTYL-L-PHENYLALANINE METHYL ESTER

摘要

One-pot prodn. of alpha-L-aspartyl-L-phenylalanine methyl ester HCL (alpha-APM.HCL) comprises; (a) formylating L-aspartic acid in a first reaction mixt. of HCOOH, Ac2O, and a secondary alcohol to yield N-formyl-L-aspartic anhydride (FAA); (b) coupling in situ with L-phenylalanine at a temp. to yield alpha-and beta-N-formyl-L-aspartyl-L-phenylalanine isomers (FAP); (c) deformylating the isomers by addn. of HCL; (d) removing residual HCOOH and Ac2O from the reaction mixt.; (e) esterifying the deformylated isomers by addn. of MeOH to the reaction mixt., to yield a mixt. of alpha- and beta-APM, HCl, of which the alpha isomer ppts.; and (f) isolating the alpha-APM.HCl.