(R)-4-氰基-3-羟基丁酸乙酯合成新方法.pdfVIP

2009 年第 29 卷 有 机 化 学 Vol. 29, 2009 第 12 期, 1997～1999 Chinese Journal of Organic Chemistry No. 12, 1997～1999 ·研究简报· (R)-4-氰基-3-羟基丁酸乙酯的合成新方法 吕世翔a 郭阳辉 b 王亚平 b 王相晶 a 向文胜*,a (a 东北农业大学生物化工系 哈尔滨 150030) (b 浙江海正药业股份有限公司 台州 318000) 摘要 研究了一条新的路线用于他汀类药物的重要中间体(R)-4-氰基-3-羟基丁酸乙酯的合成. 以廉价、易得的 L-( －)- 苹果酸为起始原料, 经酯化、还原、溴代和氰化四步反应得到目标化合物(R)-4-氰基-3-羟基丁酸乙酯, 合成总收率为 56.7%. 所有中间体和最终产物均由 ESI-MS, 1H NMR 和 13C NMR 光谱及比旋光度表征并与文献值比较. 该方法原料易 得、操作简便、收率良好, 产物容易分离纯化, 是一条适合大规模制备(R)-4-氰基-3-羟基丁酸乙酯的新合成工艺路线. 关键词 (R)-4-氰基-3-羟基丁酸乙酯; L-( －)-苹果酸; (3S)-3,4-二羟基丁酸乙酯; (S)-4-溴-3-羟基丁酸乙酯; 合成 A Novel Synthesis of (R)-4-Cyano-3-hydroxybutyric Acid Ethyl Ester Lü, Shixianga Guo, Yanghuib Wang, Yapingb Wang, Xiangjinga Xiang, Wensheng*,a a ( Department of Biochemical Engineering, Northeast Agricultural University, Harbin 150030) (b Zhejiang Hisun Pharmaceutical Co., Ltd, Taizhou 318000) Abstract A novel method for synthesis of (R)-4-cyano-3-hydroxybutyric acid ethyl ester (1), a key inter- mediate of statins, was reported. The target compound 1 was successfully prepared via esterification, reduc- tion, bromization and cyanation processes by using L-(—)-malic acid (2), which is an inexpensive and easily available starting material. The overall yield was 56.7%. The structures of intermediates and final product 1 13 were determined by ESI-MS, H NMR, C NMR techniques, opt