3-羟基-1-金刚烷甲基酮的合成  

Synthesis of 3-Hydroxy-1-acetyladamantane

作　　者：刘科江 王灰飞 王天宝 钟彩灵 向圆圆 林宏博 石忠波 胡湘南[1] LIU Ke-jiang;WANG Hui-fei;WANG Tian-bao;ZHONG Cai-ling;XIANG Yuan-yuan;LIN Hong-bo;SHI Zhong-bo;HU Xiang-nan(Pharmacy School,Chongqing Medical University,Chongqing 400016,China)

机构地区：[1]重庆医科大学药学院,重庆400016

出　　处：《合成化学》2018年第4期271-275,共5页Chinese Journal of Synthetic Chemistry

基　　金：重庆市科委资助项目(cstc2015zdcy-ztzx120003);重庆医科大学大学生科学研究与创新实验(201726)

摘　　要：改进了沙格列汀中间体3-羟基-1-金刚烷甲基酮(1)的合成路线。以金刚烷甲酸(2)为起始原料,经二氯亚砜酰氯化后与N-氯代琥珀酰亚胺(NCS)反应制得3-氯-1-金刚烷甲酰氯(3);3依次经取代,脱羧和与碱反应合成1,其结构经1H NMR,IR和MS(ESI)确证。采用星点设计-效应面法对1合成条件进行了优化。结果表明:在最佳反应条件[2 28 mmol,n(NCS)/n(2)/n(AIBN)=1/0.83/0.65,于65℃反应8 h]下,1收率70%。A route of synthesizing Saxagliptin intermediate,3-hydroxy-1-acetyladamantane(1)was improved.3-Chloro-1-adamantanecarbonyl chloride(3)was obtained by thionylchloride acylation from adamantanecarboxylic acid(2),and then reaction with N-Chlorosuccinimide(NCS).1 was synthesized by substitution,decarboxylation and alkalization from 3,respectivly.The structure was confirmed by 1 H NMR,IR and MS(ESI).Central composite design-response surface methodology was employed to optimize synthetic conditions of 1.The results demonstrated that under the optimum reaction conditions[2 28 mmol,n(NCS)/n(2)/n(AIBN)=1/0.83/0.65,reaction at 65℃for 8 h],the yield of 1 was up to 70%.

关 键 词：沙格列汀 中间体 合成 3-羟基-1-金刚烷甲基酮 工艺优化 

分 类 号：O622.4[理学—有机化学] R914.5[理学—化学]