申请人:Shionogi & Co., Ltd.
公开号:US05510506A1
公开(公告)日:1996-04-23
A process is disclosed to produce a carboxylic acid derivative of the general formula VIII!: ##STR1## wherein R.sup.1, R.sup.2, R.sup.3 and L are each as defined in the specification, characterized in that a benzyl halide is reacted with a cyano compound to give a phenylacetonitrile, which is then reacted with an alkyl nitrite in the presence of a base to give an .alpha.-hydroxyiminophenylacetonitrile, which is then reacted with an alkylating agent to give an .alpha.-alkoxyiminophenylacetonitrile, which is then hydrolyzed in the presence of a base, or is hydrated and treated with an acid, followed by hydrolysis in the presence of a base, to give an .alpha.-alkoxyiminophenylacetic acid, which is then reacted with an acid halide forming agent, or is convened into a metal salt, followed by reaction with an alkylating agent, or is reacted with a lower alcohol in the presence of an acid catalyst. According to the present invention, the reactions can be allowed to proceed under mild conditions over the whole process, and the desired carboxylic acid derivative VIII! can be produced without any facilities such as high-pressure steam equipment, high-temperature heat medium control equipment and freezing machines. In addition, there is no need to use various different solvents in the respective steps and the present process can be conducted with only one solvent, in which respect the present invention is also advantageous.
本发明揭示了一种用于生产通式VIII的羧酸衍生物的过程:##STR1##其中R.sup.1、R.sup.2、R.sup.3和L在规范中各自定义,其特征在于苄卤代烃与氰基化合物反应,得到苯乙腈,然后在碱存在下,苯乙腈与烷基亚硝酸酯反应,得到α-羟基亚氨基苯乙腈,然后与烷基化试剂反应,得到α-烷氧基亚氨基苯乙腈,然后在碱存在下水解,或水合并在酸的作用下处理,随后在碱存在下水解,得到α-烷氧基亚氨基苯乙酸,然后与酸卤化剂反应,或转化为金属盐,随后与烷基化试剂反应,或在酸催化剂存在下与低级醇反应。根据本发明,在整个过程中可以允许反应在温和条件下进行,而且可以生产所需的羧酸衍生物VIII,无需高压蒸汽设备、高温热媒控制设备和冷冻机等设施。此外,在各个步骤中无需使用各种不同的溶剂,本过程只需一个溶剂即可进行,从这个角度看,本发明也具有优势。