新药纳曲酮中间体合成方法的改进

Studies on Modifying the Synthetic Method of the New Drug, Naltrexone

较系统地探索了用氯甲酸酯类化合物脱Ｎ甲基的反应条件及中间体氨基甲酸酯的水解条件，以Ｌｅｗｉｓ及软硬酸碱理论为指导成功地改进了三溴化硼脱Ｏ甲基方法。

We have extensively explored the reaction conditions of Ndemethylation of morphinan,using chloroformate and hydrolysis of the intermediate,carbamate and found that the carbamate could be formed in high yield,using ethyl chloroformate and phenyl chloroformate,while the intermediate from the reaction of 14acetyloxycodone with αchloroethyl chloroformate without isolation could directly be hydrolyzed into secondary amine smoothly with the yield of 79%.In addition,the structures of the two new compounds Nethoxycarbonyl14acetylnoroxycodone and Nphenoxycarbonyl14acetylnoroxycodone have been determined.On the basis of the Lewis′theory on acid and base as well as softhard acid and base theory,we have succeeded in reducing the amount of boron tribromide to half of that in the former method and obtaining the same high yield by using a weak Lewis basic solvent as both an attenuating agent and a reaction medium.