阿立哌唑的合成

Synthesis of aripiprazole

目的合成抗精神病药阿立哌唑,并验证所用路线的中间体的螺环季铵盐结构。方法1-(2,3-二氯苯基)哌嗪盐酸盐与1,4-二溴丁烷反应后,再与7-羟基-3,4-2(1H)-喹喏啉酮反应。结果总收率达45%,目标化合物经核磁共振氢谱和红外确证结构,并验证了中间体结构,化学名为5,8-二氮杂螺[4,5]癸烷溴化物。结论此工艺路线生产成本低,反应条件温和、适宜工业化生产。并确证了中间体是5,8-二氮杂螺[4,5]癸烷溴化物,而非1-(4-溴丁基)-4-(2,3-二氯苯基)哌嗪。

Objective To synthesize aripiprazole,a novel antipsychotic drug.Methods aripiprazole was prepared from 1-（2,3-dichlorophenyl）piperazine hydrochloride by condensation with 1,4-dibromobutane followed by reaction with 7-hydroxy-3,4-dihydrocarbostyril.Results The overall yield was 45% aripiprazole was achieved.The process is suitable for industrial producing.the intermediate＇s structure is 8-（2,3-dichloro-phenyl）-5,8-diaza-spiro[4,5]decane bromide.Conclusion The synthetic method is economical,convenient and suitable for industrial production.It＇s proved that the intermediate＇s structure is 8-（2,3-dichloro-phenyl）-5,8-diaza-spiro[4,5]decane bromide and not 1-（4-bromo-butyl）-（2,3-dichloro-phenyl）-piperazine reported in the literature.