沙库必曲中间体(R)-2-(叔丁氧羰基氨基)-3-(联苯-4-基)丙醇的合成  

Synthesis of The Intermediate of Sacubitril,(R)-2-(t-Butoxycarbonylamino)-3-(biphenyl-4-yl)-propan-1-ol

作　　者：代祯 黄晴菲[1] 王启卫[1] DAI Zhen;HUANG Qing-fei;WANG Qi-wei(Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041, China;University of Chinese Academy of Science, Beijing 100049, China)

机构地区：[1]中国科学院成都有机化学研究所,四川成都610041 [2]中国科学院大学,北京100049

出　　处：《合成化学》2021年第4期298-302,共5页Chinese Journal of Synthetic Chemistry

基　　金：中科院“西部之光”人才培养计划资助项目。

摘　　要：采用D-酪氨酸衍生物为原料,与苯磺酰氯反应制得叔丁氧羰基保护的D-苯丙氨醇苯磺酸酯,经还原,再在5 mol%N-杂环卡宾(NHC)钯催化剂(IMes)Pd(Py)Cl作用下与苯硼酸经过Suzuki-Miyaura偶联反应得到沙库必曲重要中间体(R)-2-(叔丁氧羰基氨基)-3-(联苯-4-基)丙醇,总产率大于57%,ee值大于99%。Using D-tyrosine derivatives as raw materials,and tert-butoxycarbonyl protected D-phenylalaninol benzene sulfonate was generated in the reaction with benzyl sulfonyl chloride.After reduction,the target product was generated in the presence of 5mol%palladium catalyst(IMes)Pd(Py)Cl under the reaction of phenyl boronic acid by Suzuki-Miyaura coupling reaction.The key intermediate of Sacubitril,(R)-2-(t-Butoxycarbonylamino)-3-(biphenyl-4-yl)-propan-1-ol,was prepared with the overall yield of more than 57%.Both the chemical purity and optical purity are more than 99%.

关 键 词：沙库必曲 联苯丙氨醇 苯磺酸酯 N-杂环卡宾 Suzuki-Miyaura反应 合成 

分 类 号：O626.4[理学—有机化学] O621.3[理学—化学]