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    • 72. 发明授权
    • Preparation of N-protected .alpha.-L-aspartyl-L-phenylalanine methyl
ester
    • N-保护的α-L-天冬氨酰基-L-苯丙氨酸甲酯的制备
    • US5302743A
    • 1994-04-12
    • US823538
    • 1992-01-21
    • Toshio KatohChojiro HiguchiTakeshi OuraMasanobu AjiokaAkihiro Yamaguchi
    • Toshio KatohChojiro HiguchiTakeshi OuraMasanobu AjiokaAkihiro Yamaguchi
    • C07K5/075C07C229/00
    • C07K5/0613Y02P20/55
    • Disclosed is an improved process for the preparation of an N-protected .alpha.-L-aspartyl-L-phenylalanine methyl ester from an N-protected L-aspartic anhydride and L-phenylalanine methyl ester, the improvement which comprises employing the L-phenylalanine methyl ester in the form of a mineral acid salt thereof and conducting the reaction either (a) in an organic solvent and in the presence of a salt of an organic carboxylic acid, or (b) in an organic solvent comprising an organic carboxylic acid and in the presence of at least one member of the group consisting of an alkali metal or an alkaline earth metal inorganic base, an ammonium alkali metal or alkaline earth metal salt of an organic carboxylic acid and ammonium carbonate. The starting N-protected aspartic anhydride, e.g., N-benzyloxycarbonyl-L-aspartic anhydride, can be produced by the reaction of N-protected aspartic acid with phosgene. When the N-protecting group sibenzyloxycarbonyl and the solvent is acetic acid, the desired product can be isolated from the reaction mixture in crystalline form in high purity by adding water thereto.
    • 公开了一种由N-保护的L-天冬氨酸酐和L-苯丙氨酸甲酯制备N-保护的α-L-天冬氨酰-L-苯丙氨酸甲酯的改进方法,其改进包括使用L-苯丙氨酸甲酯 酯,其为无机酸盐,并且在有机溶剂中和有机羧酸的盐存在下进行反应,或(b)在包含有机羧酸的有机溶剂中和 存在由碱金属或碱土金属无机碱组成的组中的至少一种,有机羧酸的铵碱金属或碱土金属盐和碳酸铵。 起始的N-保护的天冬氨酸酐,例如N-苄氧基羰基-L-天冬氨酸酐可以通过N-保护的天冬氨酸与光气的反应来制备。 当N-保护基团苄氧基羰基和溶剂为乙酸时,可以通过向其中加入水从所述反应混合物中以高纯度从结晶形式中分离所需产物。