非索非那定关键中间体合成的新工艺

New Process for Synthesis of Intermediate in Production of Fexofenadine

非索非那定作为新一代的抗组胺药物,具有无镇静、无嗜睡作用,4-{1-羰基-4-[4-(羟基二苯基甲基)-1-哌啶基]丁基}-α,α-二甲基苯乙酸甲酯作为非索非那定合成中的关键中间体,是以氯代叔丁基苯为起始原料,经亲核取代反应,付-克酰基化,水解,氧化、甲基化和N-烷基化反应后而最终得到的目标产物,总收率:57.94%,化合物结构经1HNMR和MS确证。该路线原料廉价易得,操作简单,环境污染小,可实现工业化生产等优点。

Fexofenadine,as new generation of antihistamine,has no side functions of sedative and sleepiness.4-{1-hydroxy-4-[4-(hydroxydi-phenyl)-piperidine]butyl}-α,α-dimethyl methyl phenylacetate is a key intermediate in the synthesis of fexofenadine,which is the target product with an overall yield of 57.94%via nucleophilic substitution reaction,Friedel-Crafts acylation reaction,hydrolysis reaction,oxidation reaction,methesterification,N-alkylation reaction from use of neophyl chloride as original material.Thisroute has been identified by 1H NMR and MS and it has been proved that by using this route,raw material is inexpensive and easy obtained,the operation is simple,there is only slight pollution in environment and industrial scale production can be realized.