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    • 1. 发明申请
    • PROCESS FOR PREPARING O-(3-AMINO-2-HYDROXY-PROPYL)-HYDROXYMIC ACID HALIDES
    • 制备O-(3-氨基-2-羟基丙基) - 羟基酸的方法
    • WO1998043948A1
    • 1998-10-08
    • PCT/HU1997000082
    • 1997-12-05
    • BIOREX KUTATO ÉS FEJLESZTO"e; RT.ÜRÖGDI, LászlóBARABAS, MihályMARVANYOS, EdeTÖRÖK, MagdolnaCSAKAI, Zita
    • BIOREX KUTATO ÉS FEJLESZTO"e; RT.
    • C07C249/12
    • C07C259/02
    • The present invention relates to a novel process for preparing O-(3-amino-2-hydroxy-propyl)-hydroxymic acid halides of formula (I) by reacting a carboxamide oxime of formula (II) wherein R is as specified above with reactive 3-amino-2-hydroxy-propane derivative, diazotizing the O-substituted carboxamide oxime thus obtained with sodium nitrite in the presence of hydrogen halide, decomposing the diazonium salt and if desired, separating the optically active enantiomers and/or reacting the resulting base with an organic or mineral acid, wherein the carboxamide oxime of formula (II) is reacted with a 3-hydroxy azetidinium salt of formula (III) wherein R and R are as defined above and Y is a salt forming anion, in a lower alcoholic, preferably ethanolic medium optionally containing water and made alkaline with an alkali hydroxide, and before diazotizing the O-substituted carboxamide oxime intermediate obtained, the reaction mixture is neutralised and the organic solvent is removed. The process according to the invention provides the compounds of formula (I) with a higher yield compared to the prior art processes.
    • 本发明涉及式(I)的O-(3-氨基-2-羟基 - 丙基) - 羟基酰卤的制备方法,其中R 1为其中R 1为指定的式(II)的酰胺肟 用反应性3-氨基-2-羟基 - 丙烷衍生物,在卤化氢存在下,用亚硝酸钠进行重氮化O-取代的甲酰胺肟,分解重氮盐,如果需要,分离光学活性对映体和/或反应 所得到的碱与有机或无机酸反应,其中式(II)的甲酰胺肟与式(III)的3-羟基氮杂环丁烷鎓盐反应,其中R 2和R 3如上定义, - >是形成阴离子的盐,在低级醇,优选乙醇介质中,任选地含有水并用碱金属氢氧化物碱化,然后在得到的O-取代的甲酰胺肟中间体重氮化之前,将反应混合物中和,除去有机溶剂 编辑。 根据本发明的方法提供了与现有技术方法相比具有更高产率的式(I)化合物。