化学合成,医药西那卡塞中间体。
医药
合成路线 1(1. 合成:585-50-2)
产率:100%
合成条件:With hydrogen In methanol at 25℃; for 10 h;
实验步骤:例1; 3-(3-三氟甲基苯基)丙酸的制备; 将3-三氟甲基肉桂酸(0.463摩尔,100克)溶于1.0升。 加入甲醇并加入加氢容器中。 加入5%Pd / C(3克)。 将反应物料在1kg / cm2的H 2压力和250℃的温度下氢化约10小时。 反应完成后,过滤容器内容物,用甲醇(100ml)洗涤。 从过滤的物质中蒸发甲醇,得到3-(3-三氟甲基苯基)丙酸残余物(100克,产率100%)。
参考文献:
- [1] Patent: WO2010/100429, 2010, A1. Location in patent: Page/Page column 19 [2] Patent: WO2008/117299, 2008, A1. Location in patent: Page/Page column 16 [3] Beilstein Journal of Organic Chemistry, 2012, vol. 8, p. 1366 - 1373 [4] Patent: US2009/99228, 2009, A1. Location in patent: Page/Page column 10-11; 18 [5] Patent: EP2013209, 2011, B1. Location in patent: Page/Page column 22 [6] Patent: US4328355, 1982, A [7] Patent: WO2012/7954, 2012, A1. Location in patent: Page/Page column 11 [8] European Journal of Organic Chemistry, 2012, # 15, p. 2990 - 3000
合成路线 2(2. 合成:585-50-2)
产率:99.4%
合成条件:With palladium on activated charcoal; hydrogen; sodium carbonate In water at 25℃; for 3 h;
实验步骤:向2L四颈烧瓶中加入216.0g间三氟甲基肉桂酸(1.0mol)。搅拌溶解1L水和53.0g碳酸钠(0.5mol),转移至氢化槽中,然后加入10g在加氢槽中加入3wt%的钯 - 碳催化剂,氮气置换后,氢气将反应物在25±5℃和0.2-0.3MPa的压力下保温3小时。反应完成后,过滤混合物,用2N稀盐酸将滤液调至pH3-4,沉淀出白色固体,然后加入1L。甲苯萃取一次,分液,有机层用1L水洗涤一次分离各层,合并有机层。在55±5℃的温度下减压浓缩,得到无色透明油状物。最后,将其自然冷却至室温(20±5℃)。获得216.7g三氟甲基苯基白色固体之间的罗匹酸,产率为99.4%。
参考文献:
- [1] Tetrahedron Letters, 2008, vol. 49, # 1, p. 13 - 15 [2] Patent: CN107963965, 2018, A. Location in patent: Paragraph 0024-0026; 0028-0035 [3] Synthetic Communications, 2008, vol. 38, # 10, p. 1512 - 1517 [4] Tetrahedron Letters, 2015, vol. 56, # 30, p. 4468 - 4471 [5] Patent: WO2008/58235, 2008, A2. Location in patent: Page/Page column 23 [6] Tetrahedron Letters, 2004, vol. 45, # 45, p. 8355 - 8358 [7] Patent: CN108358778, 2018, A. Location in patent: Page/Page column 6-10 [8] Bioorganic and Medicinal Chemistry Letters, 2000, vol. 10, # 14, p. 1519 - 1522 [9] Patent: US2007/259964, 2007, A1. Location in patent: Page/Page column 3; 5 [10] Patent: WO2008/58235, 2008, A2. Location in patent: Page/Page column 26-28 [11] Patent: EP1990333, 2008, A1. Location in patent: Page/Page column 6-7; 9; 10; 11 [12] Patent: WO2008/35381, 2008, A2. Location in patent: Page/Page column 24 [13] Patent: EP2168944, 2010, A1. Location in patent: Page/Page column 49