Process for production of aspartyl dipeptide ester derivatives

A process for producing an aspartyl dipeptide ester derivative represented by formula (2):

• 8
• wherein in formula (2) R1, R2, R3, R4 and R5 are each independently of each other a substituent selected from the group consisting of a hydrogen atom, a hydroxyl group, an alkoxy group having 1 to 3 carbon atoms, an alkyl group having 1 to 3 carbon atoms, and a hydroxyalkyloxy group having 2 or 3 carbon atoms, wherein R1 and R2, or R2 and R3, together may be combined to form a methylenedioxy group, wherein said derivative may be in any form of the free form and the salt form,
• said process comprising:
• reductively alkylating aspartame with an aldehyde represented by formula (1), and hydrogen in the presence of a catalyst and a base:
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• wherein in formula (1) R1, R2, R3, R4 and R5 are each independently of each other a substituent selected from the group consisting of a hydrogen atom, a hydroxyl group, an alkoxy group having 1 to 3 carbon atoms, an alkyl group having 1 to 3 carbon atoms, a benzyloxy group and a hydroxyalkyloxy group having 2 or 3 carbon atoms, wherein R1 and R2, or R2 and R3, together may be combined to form a methylenedioxy group, and wherein the hydroxyl group may denote a substituent group in its derivative form in which the hydrogen atom in said hydroxyl group has been replaced by a metal atom.