Studies On The Synthesis Of Two Impurities In Epinastine Hydrochloride

Epinastine hydrochloride is an important drug for the treatment of allergic disease.During the production of epinastine hydrochloride,however,several impurities are produced inevitably,which would be harmful for human body.Therefore,the exploration of the impurities in drugs remains an urgent challenge.This thesis aims at the studies on the synthesis of two impurities in epinastine hydrochloride,and the main contents could be divided into the following three parts.Chapter One:Overview of epinastine hydrochloride.The general situation,structure feature and the development on the synthesis of epinastine hydrochloride were briefly described.Chapter Two:Studies on the synthesis of two impurities in epinastine hydrochloride.Using cheap and readily available 4-chloro aniline(or 4-bromo aniline)and as starting materials,the synthesis of two impurities in epinastine hydrochloride was achieved in 7 steps with 15.3%and 15.8%overall yield,respectively.These results would be useful for the precise analysis of the impurities in epinastine hydrochloride during the production,accordingly,may result in the appearance of a new method that can control the content of impurities in a safe and reasonable extent.Chapter Three:The studies on the synthesis of(Z)-3-((tert-butyldimethylsilyl)oxy)-2,4,6-trimethyl-5-oxooct-6-enoic acid.The synthesis of(Z)-3-((tert-butyldimethylsilyl)oxy)-2,4,6-trimethyl-5-oxooct-6-enoic acid was explored.The key building block 97 was obtained using Grignard reaction and Swern oxidation as the key reactions..