摘 要 本研究建立了一条沙库必曲关键中间体(R)-叔丁基(1-([1，1’-联苯]-4-基)-3-羟基丙烷-2-基)氨基甲酸酯(1)的新合成路线。以D-苯丙氨酸作为原料，经过碘代、还原、Boc保护、Suzuki反應制得1。该路线的手性中心是由廉价易得的起始原料引入，避免了现有技术后期拆分的物料损失，有效降低了成本，提高了产品质量；反应步骤明显缩短，反应条件温和，避免使用剧毒品以及危险系数高的试剂，绿色环保，适合工业化生产。总收率51.98%，产品纯度99.86%，手性纯度99.98%。

    关键词 沙库必曲 产业化 合成

    中图分类号：O623.42 文献标志码：A 文章编号：1006-1533(2022)09-0073-04

    引用本文 于立国. 沙库必曲关键中间体的合成工艺改进[J]. 上海医药， 2022， 43(9)： 73-76.

    Improvement of synthetic process for key sacubitril intermediate

    YU Liguo

    (Changzhou Pharmaceutical Factory， Shanghai Pharmaceutical Group， Changzhou 213018， China)

    ABSTRACT A novel route for the synthesis of key intermediate (R)-tert-butyl(1-([1，1’-biphenyl]-4-yl)-3-hydroxypropan-2-yl)carbamate (1) was established. 1 was prepared by iodination， reduction， Boc protection and Suzuki reaction using D-phenylalanine as raw material. The chiral center of this route was introduced from inexpensive and readily available starting raw materials， which can avoid material loss in the later resolution of prior art ......