布瓦西坦合成工艺改进  

Improved Synthesis of Buvasetam

作　　者：龙明渊 丁丽 LONG Ming-yuan;DING Li(Zhejiang Menovo Pharmaceutical Co.,Ltd.,Shangyu 312369,China;Tianxiangyutong(Shanghai)Quality Service Co.,Ltd.,Shanghai 200010,China)

机构地区：[1]浙江美诺华药物化学有限公司,浙江上虞312369 [2]天祥域通(上海)质量服务有限公司,上海200010

出　　处：《化工管理》2021年第23期153-154,共2页Chemical Engineering Management

摘　　要：文章以对甲苯亚磺酸钠为起始原料,经过偶联、加成环合、开环偶联、开环酰胺化、环合、还原脱羟基、脱甲苯磺酰基来制备布瓦西坦。其中,中间体(S)-4-丙基-3-对甲苯磺酰-二氢呋喃-2-酮)的合成以对甲苯磺酰乙腈为原料,与R-环氧氯丙烷进行加成环合,再与乙基氯化镁开环偶联合成,该工艺路线原料易得,产物收率高;中间体3-甲苯磺酰基布瓦西坦,采用TEMPO作为偶联剂,高碘酸钠作为质子化试剂,有效促进内酰胺的合成,再经过三乙基硅烷和内酰胺环上的羟基形成氧硅烷活性中间体,然后经过镁粉还原,脱羟基合成。与现有技术相比,该工艺路线原料成本低,工艺安全环保,制备的产品与同类产品相比品质佳、性能优异,市场需求量大,竞争力强。In this paper,sodium p-toluenesulfonate was used as the starting material to prepare busracetam through coupling,addition cyclization,ring opening coupling,ring opening amidation,cyclization,reductive dehydroxylation and demethylenesulfonyl.Among them,the intermediate(s)-4-propyl-3-p-toluenesulfonyl-dihydrofuran-2-one)was synthesized from p-toluenesulfonyl acetonitrile by cyclization with R-epichlorohydrin and ring opening coupling with ethyl magnesium chloride.The intermediate,3-toluenesulfonylbuvasitam,was synthesized by using tempo as coupling agent and sodium periodate as protonation reagent,which effectively promoted the synthesis of lactam.Then,the active intermediate of oxysilane was formed by triethylsilane and hydroxyl groups on the lactam ring,which was reduced by magnesium powder and dehydroxylated.Compared with the existing technology,the process has the advantages of low cost of raw materials,safe and environmental protection,good quality,excellent performance,large market demand and strong competitiveness.

关 键 词：布瓦西坦 合成 工艺改进 

分 类 号：R917[医药卫生—药物分析学]