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替卡格雷是一种口服选择性小分子抗凝血药,不需要通过代谢激活,自身具有抗血小板活性。(1R,2S)-2-(3,4-二氟苯基)环丙胺是合成替卡格雷的一个关键中间体。该文在文献报道的合成路线基础上对其中关键步骤——不对称Corey-Chaykovsky环丙烷化反应进行了研究,筛选出最优反应条件:以L-薄荷醇为手性辅剂,三甲基碘化锍盐为硫叶立德试剂,二甲亚砜和四氢呋喃为混合溶剂,温度为10～12℃,质量分数10%的碘化亚铜为催化剂时,反应收率为60.5%;合成(1R,2S)-2-(3,4-二氟苯基)环丙胺5步总收率为20.0%。
Ticagrelor is an oral, selective small-molecule anticoagulant that does not require metabolic activation and has anti-platelet activity itself. (1R, 2S) -2- (3,4-difluorophenyl) cyclopropanamine is a key intermediate in the synthesis of ticagrelor. Based on the synthetic routes reported in the literature, asymmetric Corey-Chaykovsky cyclopropanation was studied, and the optimum reaction conditions were screened out: L-menthol as chiral auxiliary, trimethyl The sulfonium iodide salt is sulfur ylide reagent, and the reaction yield is 60.5% when dimethyl sulfoxide and tetrahydrofuran are mixed solvents at the temperature of 10-12 DEG C and the mass fraction of 10% copper iodide is used as a catalyst; the synthesis of (1R, 2S) -2- (3,4-difluorophenyl) cyclopropanamine The overall 5-step yield was 20.0%.