申请人:SHIONOGI & CO., LTD.
公开号:EP0658541A1
公开(公告)日:1995-06-21
A process for producing a carboxylic acid derivative represented by general formula [VIII], (wherein R¹, R², R³ and L are each as defined in the specification), which comprises reacting a benzyl halide with a cyano compound to give a phenylacetonitrile, reacting the nitrile with an alkyl nitrite in the presence of a base to give an α-hydroxyiminophenylacetonitrile, reacting the hydroxy nitrile with an alkylating agent to give an α-alkoxyiminophenylacetonitrile, hydrolyzing the alkoxy nitrile in the presence of a base, optionally after hydration and acid treatment, to give an α-alkoxyiminophenylacetic acid, and finally reacting the acid with a halogenating agent, or converting the acid into a corresponding metal salt and reacting the salt with an alkylating agent, or reacting the acid with a lower alcohol in the presence of an acidic catalyst. According to this process, the reactions can be advanced through the respective steps under mild conditions, and the target derivative [VIII] can be produced even without resort to high-pressure steam equipment, high-temperature heat medium equipment, refrigerator, and so forth. Further, this process is advantageous in that only a single solvent will suffice without the necessity for using various solvents according to the respective steps.
一种生产通式[VIII]所代表的羧酸衍生物的工艺(其中R¹、R²、R³和L各自如说明书中所定义),该工艺包括将卤化苄基与氰基化合物反应,得到苯乙腈、在碱存在下,使腈与亚硝酸烷基酯反应,得到 α-羟基亚氨基苯乙腈,使羟基腈与烷化剂反应,得到 α-烷氧基亚氨基苯乙腈、在碱存在下,水解烷氧基腈(可选择在水合和酸处理后),得到 α-烷氧基亚氨基苯乙酸,最后使酸与卤化剂反应,或将酸转化为相应的金属盐并使盐与烷 化剂反应,或在酸性催化剂存在下使酸与低级醇反应。根据这种工艺,反应可以在温和的条件下通过相应的步骤进行,即使不使用高压蒸汽设备、高温热媒设备、冰箱等,也可以生产出目标衍生物[VIII]。此外,该工艺的优点还在于只需使用一种溶剂即可,而无需根据不同的步骤使用不同的溶剂。