Process for producing N2-(1(S)-carboxy-3-phenylpropyl)-L-lysyl-L-proline

A process for producing N2-(1(S)-carboxy-3-phenylpropyl) L-lysyl-L-proline of the formula (2):

• from an N2- (1(S)-alkoxycarbonyl-3-phenylpropyl)-N6-trifluoroacetyl L-lysyl-L-proline of the general formula (1):
• wherein R represents an alkyl group,
• which comprises:
• the first step:
• subjecting the N2-(1(S)-alkoxycarbonyl 3-phenylpropyl) -N6-trifluoroacetyl-L-lysyl-L-proline (1) to alkali hydrolysis in a solvent system being selected from among a mixed solution composed of water and a hydrophilic organic solvent, and water using an inorganic base in an amount of n molar equivalents (n ≧ 3) per mole of the above compound (1),
• the second step:
• neutralizing the hydrolysis product using an inorganic acid in an amount of (n − 1) to n molar equivalents (n ≧ 3) and
• separating and removing the inorganic salt formed from the above inorganic base and inorganic acid in the reaction mixture by causing the same to precipitate out from a solvent system suited for decreasing the solubility of the inorganic salt,
• said solvent system being selected from a hydrophilic organic solvent, a mixed solvent composed of water and a hydrophilic organic solvent, and water, and
• the third step:
• causing the N2-(1(S)-carboxy-3-phenylpropyl) L-lysyl-L-proline (2) existing in the mixture after removal of the inorganic salt to crystallize out from a solvent system at the isoelectric point thereof,
• said solvent system being selected from a hydrophilic organic solvent, a mixed solvent composed of water and a hydrophilic organic solvent, and water, and
• thereby recovering the N2- (1(S)-carboxy-3-phenylpropyl) L-lysyl-L-proline (2) in the form of crystals while retaining the salts mainly comprising the trifluoroacetic acid-derived organic acid salt in a state dissolved in the mother liquor.