盐酸他喷他多的合成  

Synthesis of Tapentadol Hydrochloride

作　　者：马慧[1] 冯文化[1] 梁玉华[1] 

机构地区：[1]北京协和医学院药物研究所,北京100050

出　　处：《中国医药工业杂志》2010年第9期641-644,共4页Chinese Journal of Pharmaceuticals

摘　　要：间甲氧基苯丙酮与二甲胺盐酸盐发生Mannich反应生成消旋3-二甲胺基-1-(3-甲氧基苯基)-2-甲基-1-丙酮(13),经结晶诱导的非对映异构体转化得到S-型化合物14后,经格氏反应、酰化及催化氢解得到(2R,3R)-2-甲基-3-(3-甲氧基苯基)-N,N-二甲基戊胺,最后经脱保护基、与盐酸成盐得到中枢镇痛药盐酸他喷他多,总收率约52%。The central analgesics tapentadol hydrochloride was synthesized from 1-（3-methoxyphenyl）-1-propanone by Mannich reaction with dimethylamine hydrochloride to obtain racemic 3-dimethylamino-1-（3-methoxyphenyl）-2-methylpropan-1-one（13）,which was subjected to crystallization-induced diastereomer transformation,Grignard reaction,acylation and catalytic hydrogenolysis to give （2R,3R）-2-methyl-3-（3-methoxyphenyl）-N,N-dimethylpentanamine,followed by deprotection and salt formation with an overall yield of about 52%.

关 键 词：他喷他多 中枢镇痛药 阿片μ受体激动剂 肾上腺素能递质摄取抑制剂 结晶诱导 合成 

分 类 号：R971.1[医药卫生—药品]