比拉斯汀关键中间体的合成

Synthesis of Key Intermediates of Bilastine

以2-[1-（4-溴苯基）-1-甲基乙基]-4,5-二氢-4,4-二甲基唑为原料,通过与二溴乙烷的格氏反应得到4-[1-（5,5-二氢-4,4-二甲基-2-唑基）-1-甲基乙基]-2-苯乙基溴,再与2-（4-哌啶基）-1H-苯并咪唑在碱性条件下经亲核取代得到比拉斯汀中间体2-（2-（4-（2-（4-（1H-苯并咪唑-2-基）哌啶-1-基）乙基）苯基）丙-2-基）-4,4-二甲基4,5-二氢唑,总收率63%。新工艺不仅避免了正丁基锂、环乙烷等危险试剂的使用,而且降低了安全隐患和环境污染,简化了实验步骤,且操作简便、收率高,适合工业化生产。

2-（2-（4-Bromophenyl） propan-2-yl）-4,4-dimethyl-4,5-dihydrooxazole was used as the starting material,2-（2-（4-（2-bromoethyl） phenyl） propan-2-yl）-4,4-dimethyl-4,5-dihydrooxazole was synthesized via Grignard reaction by reacted with 1,2-dibromoethane.The brominated product further reacted with 2-（piperidin-4-yl）-1 H-benzo imidazole in the presences of base to afford 2-（2-（4-（2-（4-（1 H-benzo imidazol-2-yl） piperidin-1-yl） ethyl） phenyl） propan-2-yl）-4,4-dimethyl-4,5-dihydrooxazoe the key intermediate of bilastine with an overall yield of 63%.The process avoids the use of fuming N-butyllithium,ethylene oxide and other dangerous reagents,reduces potential safety hazard and environmental pollution.Furthermore,this process also has some other advantages such as simple operation,high yield,and it is suitable for industrial production.