依巴斯汀合成工艺改进

Improved Synthesis of Ebastine

本研究对依巴斯汀(1)的合成工艺进行了改进。以价格低廉的二苯甲酮(5)为原料,经硼氢化钾还原得二苯甲醇(6);6与4-羟基哌啶(3)经脱水缩合得4-二苯甲氧基哌啶(4),该步反应采用将化合物6的固体一次性加至50℃的化合物3和对甲苯磺酸的甲苯溶液中进行反应,简化操作,收率也由文献的86%提高至95%。4再与4-氯-1-(4-叔丁基苯基)-1-丁酮(2)缩合,并经与枸橼酸成盐分离纯化得终产物1,纯度99.9%,总收率41%(以5计)。改进后的工艺原料价廉易得、成本低,反应条件温和,操作简便,适于工业化生产。

An improved synthetic process of ebastine （1） was reported. The cheap raw material benzophenone （5） was reduced by potassium borohydride to give benzhydrol （6）, and then the latter reacted with 4-hydroxypiperidine （3） via dehydration to give 4-（benzhydryloxy）piperidine （4）. In this step, compound 6 was added into the toluene solution of compound 3 and p-toluenesulfonic acid directly at 50 ℃, the operation procedure was simplified and the yield was increased from 86% to 95~. Then the title compound 1 was obtained after the condensation of 4 and 4-chloro-1- （4-tert-butylphenyl）-l-butanone （2）, followed by purification via salification with citric acid, with an overall yield of 41% （based on 5） and a purity of 99.9 %. The improved synthetic process had some advantages, such as low cost, mild reaction conditions, and simple work-up, which make it easy for industrial production.