PROCESS FOR PRODUCTION OF OPTICALLY ACTIVE 3-AMINO-2 -HYDROXYPROPIONIC CYCLOPROPYLAMIDE DERIVATIVES AND SALTS THEREOF
申请人:Kaneka Corporation
公开号:EP2039689A1
公开(公告)日:2009-03-25
An objective of the present application is to provide an industrially practicable method for producing an optically-active 3-amino-2-hydroxypropionic cyclopropylamide derivative or salt thereof from an inexpensive easily-available starting material. The derivative or salt thereof is useful as an intermediate for a medicine. It is also intended by the present application to provide a useful intermediate of the derivative. The objective is attained by the following method. First, an easily-available 2-halo-3-oxopropionic acid derivative is asymmetrically reduced, and then epoxidated to produce an optically-active epoxycarboxylic acid derivative. Next, the derivative is converted into an optically-active epoxyamide derivative by reaction with cyclopropylamine, and then reacted with a nitrile to obtain an optically-active oxazolinamide derivative. Subsequently, selective acid solvolysis of the oxazoline skeleton gives the optically-active 3-amino-2-hydroxypropionic cyclopropylamide derivative or salt thereof.
本申请的目的是提供一种工业上可行的方法,利用廉价易得的起始原料生产具有光学活性的 3-氨基-2-羟基丙酰基环丙基酰胺衍生物或其盐。该衍生物或其盐可用作药物的中间体。本申请的另一个目的是提供一种有用的衍生物中间体。通过以下方法可以达到目的。首先,将一种易得的 2-卤代-3-氧代丙酸衍生物进行不对称还原,然后环氧化,生成一种具有光学活性的环氧羧酸衍生物。接着,该衍生物与环丙胺反应转化为光学活性环氧酰胺衍生物,然后与腈反应得到光学活性噁唑啉酰胺衍生物。随后,对噁唑啉骨架进行选择性酸溶解,得到具有光学活性的 3-氨基-2-羟基丙酸环丙基酰胺衍生物或其盐。