盐酸他喷他多的合成  

Synthesis of tapentadol hydrochloride

作　　者：程青芳[1,2] 王启发[1] 廖云鹏[1] 帅美[1] 

机构地区：[1]淮海工学院化工学院,连云港222005 [2]江苏省海洋资源开发研究院,连云港222001

出　　处：《中国新药杂志》2013年第14期1691-1693,共3页Chinese Journal of New Drugs

基　　金：江苏省"六大人才高峰"高层次人才项目;连云港市工业攻关资助项目(CG1106)

摘　　要：目的:改进中枢镇痛新药盐酸他喷他多的合成工艺。方法:以外消旋的1-二甲氨基-2-甲基-3-戊酮为原料,经拆分、格氏反应、酰化及催化氢解制得重要中间体(2R,3R)-2-甲基-3-(3-甲氧基苯基)-N,N-二甲基戊胺(4)。4再经脱保护基、与盐酸成盐制得盐酸他喷他多。结果:工艺的总收率为57.8%,中间体及目标化合物的结构经质谱、核磁共振谱等确证。结论:本方法操作简便、成本较低、条件温和、步骤少,适合工业化生产。Objective： To improve the synthesis of the new central analgesic tapentadol hydrochloride.Methods： The important intermediate（2R,3R）-2-methyl-3-（3-methoxyphenyl）-N,N-dimethylpentanamine（4） was prepared from racemic 1-dimethylamino-2-methylpentan-3-one by resolution,Grignard reaction,acylation and catalytic hydrogenolysis.Tapentadol hydrochloride was synthesized from 4 by deprotection and salification with hydrochloride.Results： The total yield was 57.8%,and the structures of intermediates and target compound were identified by MS and 1H-NMR.Conclusion： This improved method can be used industrially because of simple operation,a lower cost,and mild condition.

关 键 词：盐酸他喷他多 中枢镇痛药 肾上腺素能递质摄取抑制剂 合成 

分 类 号：R914.5[医药卫生—药物化学]