(R)-3-氨基-4-(2,4,5-三氟苯基)丁酸的合成  

Synthesis of(R)-3-Amino-4-(2,4,5-trifluorophenyl)butanoic Acid

作　　者：应佳妮 盛振华 YING Jia-ni;SHENG Zhen-hua(Academy of Chinese Medical Sciences,Zhejiang Chinese Medical University,Hangzhou 310014,China)

机构地区：[1]浙江中医药大学中医药科学院,浙江杭州310014

出　　处：《化学试剂》2020年第10期1255-1259,共5页Chemical Reagents

基　　金：浙江中医药大学校级科研基金项目(2019ZY30)。

摘　　要：以2,4,5-三氟苯乙酸为起始原料,与2,2-二甲基-1,3-二烷-4,6-二酮缩合后经苯甲醇醇解得到3-氧代-4-(2,4,5-三氟苯基)丁酸苄酯,与(R)-α-苯乙胺缩合后经不对称还原及脱除苄基保护基得到西他列汀关键手性中间体标题化合物,总产率59.6%,纯度98.5%,其结构经1HNMR、13CNMR、MS(ESI)和HR-MS(ESI)确证。工艺具有反应条件温和、操作简单、产率高等优点,适合工业化生产。The title compound has been obtained via five steps from 2,4,5-trifluorophenylacetic acid,which was easily transformed into 3-oxo-4-(2,4,5-trifluorophenyl)butyric acid benzyl ester by condensation with 2,2-dimethyl-1,3-dioxane-4,6-dione and then alcoholysis in benzyl alcohol.Treatment of methyl 3-oxo-4-(2,4,5-trifluorophenyl)butanoate with(R)-α-phenylethylamine,followed by asymmetric reduction with sodium borohydride(NaBH4)provided diastereoisomers.The chiral auxiliary group and benzyl protecting group were removed by hydrogenation to obtain the key intermediate with the total yield of 59.6%and the purity of 98.5%.The structure was confirmed by 1HNMR,13CNMR,MS(ESI)and HR-MS(ESI).The experimental results showed that the process exhibited mild reaction conditions,simple operation and high yield,which was suitable for industrial production.

关 键 词：2 4 5-三氟苯乙酸 (R)-3-氨基-4-(2 4 5-三氟苯基)丁酸 西他列汀 关键手性中间体 合成 

分 类 号：O625.42[理学—有机化学]