丁苯那嗪的绿色合成工艺  

A novel process for synthesis of tetrabenazine

作　　者：李晓敏[1] 陈正平[1] 刘春仪[1] 唐婕[1] 

机构地区：[1]江苏省原子医学研究所卫生部核医学重点实验室江苏省分子核医学重点实验室,江苏无锡214063

出　　处：《化工学报》2012年第2期567-571,共5页CIESC Journal

基　　金：国家自然科学基金项目(30970844);江苏省自然科学基金项目(BK2010155);江苏省医学重点人才基金~~

摘　　要：引言丁苯那嗪（tetrabenazine,商品名Xenazine,Nitoman）（1）是用于治疗亨廷顿舞蹈病（Hun-tington’s disease,HD）的药物。Tetrabenazine was approved as the first drug to treat chorea associated with Huntington＇s disease in USA in 2008.A two-step process employing water as reaction medium method was proposed for synthesis of tetrabenazine.The first step in the process was synthesis of 3-dimethylaminomethyl-5-methyl-hexan-2-one from 5-methyl-2-hexanone via Mannich reaction,and the second step was that the intermediate was reacted further with 6,7-dimethoxy-3,4-dihydroisoquinoline hydrochloride in water at 90℃ catalyzed by triethylbenzylammonium chloride（TEBAC）to give the target compound.The effect of reaction conditions on the yield was investigated.The optimal reaction conditions obtained（temperature,time,molar yield）were as follows： Mannich reaction,reflux for 5 h,55%;amine exchange,90℃ for 3.5 h,68%.The chemical structure of the target product with 98% HPLC purity was characterized by 1H NMR,IR,MS and elemental analyses.The process is of potential value for commercial application because of cheap and available materials,milder conditions,shorter reaction time,simple operations and environmental friendly.

关 键 词：绿色化学 丁苯那嗪 亨廷顿舞蹈病 药物合成 水介质 

分 类 号：O626.324[理学—有机化学] TQ463.54[理学—化学]