PROCESS FOR THE PREPARATION OF N2-(1(S)-CARBOXY-3-PHENYLPROPYL);L-LYSYL-L-PROLINE

摘要

A process for preparing N2-(1(S)-carboxy-3-phenylpropyl)-L-lysyl-L-proline (2) easily, efficiently and industrially advantageously, which comprises: the first step of conducting the alkaline hydrolysis of an N2-(1(S)-alkoxycarbonyl-3-phenylpropyl)-N6-trifluoroacetyl-L-lysyl-L-proline (1) by the use of n molar equivalents (wherein n 3) of an inorganic base per mol of the compound (1) either in a mixture of water with a hydrophilic organic solvent or in water; the second step of neutralizing the resulting reaction mixture with (n-1) to n molar equivalents (wherein n 3) of an inorganic acid, replacing the solvent system by a suitable one to thereby precipitate an inorganic salt formed by the above neutralization, and separating and removing the salt; and the third step of crystallizing the compound (2) present in the liquid mixture left after the above removal of the salt at its isoelectric point and recovering the compound (2) as a crystal, while salts mainly comprising organic acid salts resulting from trifluoroacetic acid remain dissolved in the mother liquor.