甲氧普烯中手性杂质的合成  

Synthesis of Chiral Impurity in Methoprene

作　　者：蔡建光 阳凯 林塘焕 王灵辉 王冠 CAI Jianguang;YANG Kai;LIN Tanghuan;WANG Linghui;WANG Guan(Zhejiang Hisun Pharmaceutical Co.,Ltd.,Taizhou 318000)

机构地区：[1]浙江海正药业股份有限公司,浙江台州318000

出　　处：《中国医药工业杂志》2021年第11期1468-1471,共4页Chinese Journal of Pharmaceuticals

摘　　要：为更好地控制甲氧普烯原料药的质量,设计路线合成了甲氧普烯(R)-型异构体(7R,2E,4E)-11-甲氧基-3,7,11-三甲基十二碳-2,4-二烯酸异丙酯(2)。从廉价易得的(R)-2-异亚丙基-5-甲基环己酮(3)出发,通过氯化氢气体发生烯烃加成反应,所得产物在碱性环境下发生共价键断裂得(R)-3,7-二甲基-6-辛烯酸(5),5经一系列反应制得(R)-甲氧基香茅醛(8)。8在碱性条件下与3-甲基戊烯二酸二甲酯(9)缩合得(R)-4-(7-甲氧基-3,7-二甲基亚辛基)-3-甲基戊-2-烯二酸(10)。10经脱羧、异构化、铵化和酯化反应制得2,产物纯度大于94%。In order to perform the quality control of methoprene,its(R)-isomer,(7R,2E,4E)-11-methoxy-3,7,11-trimethyldodecadienoic acid isopropyl ester(2),was synthesis.(R)-3,7-Dimethyl-6-octenoic acid(5)was prepared from inexpensive and easily available(R)-5-methyl-2-(propan-2-ylidene)cyclohexan-1-one(3)via substitution reaction by HCl(g)and cleavage of covalent bands in an alkaline environment,then(R)-7-methoxy-3,7-dimethyloctenal(8)was prepared from 5 by a series of chemical reactions.(R)-4-(7-Methoxy-3,7-dimethyloctylidene)-3-methylpent-2-enedioic acid(10)was synthesized by 8 and dimethyl 3-methylpent-2-enedioate(9)under basic conditions.Then the target product 2 was prepared by a series of chemical reactions include decarboxylation,isomerization,ammonization and esterification.This reported synthesis route was efficient to prepare the chiral compound 2 with a purity of more than 94%.

关 键 词：甲氧普烯 (R)-型异构体 合成工艺 有关物质 质量控制 

分 类 号：TQ460.6[化学工程—制药化工]