PREPARATION METHOD OF APREMILAST AND INTERMEDIATE THEREOF

摘要

Provided are a preparation method of Apremilast and intermediates thereof. Also provided is an Apremilast intermediate shown by Formula III, wherein Apremilast is obtained with the compound of Formula III sequentially reacting with methyl sulfinate, reductively-aminated, salified with asymmetric acids, and reacting with 3-acetyl amino phthalic anhydride. The method for preparing Apremilast provided in the present application can avoid using an n-butyl lithium n-hexane solution, which reduces the production cost, facilitates the operating process, improves security in the industrial production, and is more suitable for industrialized continuous production. The yield of the method for preparing 3-acetyl amino phthalic anhydride provided in the present application is increased to 81% which has higher yield and is extremely suitable for industrialized production of Apremilast.