化学合成。
化学合成
合成路线 1（1. 合成：42058-59-3）
产率：100%
合成条件：for 18 h; Heating / reflux
实验步骤：将（3-羟基 - 苯基） - 乙酸（5.0g，32.86mmol）在甲醇（100mL）中搅拌并加入浓缩的（98％）硫酸（3.0mL）。 将混合物加热至回流18小时。 将反应冷却并浓缩。 将残余物用水（100mL）稀释，并用乙酸乙酯（3×50mL）萃取。 合并的萃取液用无水硫酸镁干燥，过滤并浓缩，得到标题化合物，为橙色油状物，5.46g，100％。 MS M ++ 1 167.该结构通过1H NMR光谱确认。
参考文献：
- [1] Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 21, p. 5488 - 5492 [2] Patent: WO2004/63155, 2004, A1. Location in patent: Page 58 [3] Patent: WO2005/66136, 2005, A1. Location in patent: Page/Page column 51 [4] Patent: WO2005/19190, 2005, A2. Location in patent: Page/Page column 51 [5] Patent: WO2005/103050, 2005, A2. Location in patent: Page/Page column 168 [6] Patent: WO2007/56366, 2007, A2. Location in patent: Page/Page column 30 [7] Patent: WO2004/41813, 2004, A1. Location in patent: Page 113-114 [8] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 19, p. 5617 - 5621 [9] Patent: WO2007/56497, 2007, A1. Location in patent: Page/Page column 26 [10] Chemical and Pharmaceutical Bulletin, 2011, vol. 59, # 8, p. 1029 - 1037 [11] Patent: WO2005/105780, 2005, A2. Location in patent: Page/Page column 72 [12] Patent: WO2005/60958, 2005, A1. Location in patent: Page/Page column 144-145 [13] Patent: US2007/219193, 2007, A1. Location in patent: Page/Page column 12; 21-22 [14] Patent: WO2003/82802, 2003, A1. Location in patent: Page/Page column 41 [15] Patent: WO2004/43939, 2004, A1. Location in patent: Page 56 [16] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 19, p. 5617 - 5621 [17] Organic Letters, 2012, vol. 14, # 23, p. 5820 - 5823 [18] Patent: WO2004/101528, 2004, A2. Location in patent: Page 227 [19] Patent: US2003/225122, 2003, A1. Location in patent: Page 21 [20] Patent: US2009/30082, 2009, A1. Location in patent: Page/Page column 7; Sheet 4/5 [21] Journal of Medicinal Chemistry, 1999, vol. 42, # 21, p. 4394 - 4404 [22] ChemMedChem, 2017, vol. 12, # 20, p. 1693 - 1696 [23] European Journal of Medicinal Chemistry, 2014, vol. 86, p. 714 - 723 [24] Journal of Medicinal Chemistry, 2018, vol. 61, # 7, p. 2753 - 2775 [25] Patent: WO2010/138901, 2010, A1. Location in patent: Page/Page column 109 [26] Patent: WO2005/102997, 2005, A1. Location in patent: Page/Page column 40 [27] Bioorganic and Medicinal Chemistry, 2000, vol. 8, # 7, p. 1757 - 1766 [28] European Journal of Organic Chemistry, 2003, # 17, p. 3407 - 3411 [29] Journal of Medicinal Chemistry, 2017, vol. 60, # 1, p. 441 - 457 [30] Advanced Synthesis and Catalysis, 2017, vol. 359, # 6, p. 959 - 965 [31] Journal of Medicinal Chemistry, 2005, vol. 48, # 13, p. 4312 - 4331 [32] Journal of Organic Chemistry, 2006, vol. 71, # 15, p. 5594 - 5598 [33] Patent: EP1602642, 2005, A1. Location in patent: Page/Page column 22-23 [34] Patent: US2005/288318, 2005, A1. Location in patent: Page/Page column 11 [35] Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 20, p. 6125 - 6128 [36] Patent: WO2011/51375, 2011, A1. Location in patent: Page/Page column 14 [37] Patent: EP2316820, 2011, A1. Location in patent: Page/Page column 7 [38] Patent: WO2013/78123, 2013, A1. Location in patent: Page/Page column 104 [39] European Journal of Medicinal Chemistry, 2015, vol. 93, p. 156 - 171 [40] ACS Medicinal Chemistry Letters, 2017, vol. 8, # 3, p. 287 - 292 [41] Patent: WO2009/102893, 2009, A2. Location in patent: Page/Page column 102 [42] Patent: WO2009/145989, 2009, A2. Location in patent: Page/Page column 90 [43] Patent: WO2004/101528, 2004, A2. Location in patent: Page 143
合成路线 2（2. 合成：42058-59-3）
产率：100%
合成条件：With sulfuric acid In methanol for 18 h; Heating / reflux
实验步骤：将（3-羟基 - 苯基） - 乙酸（5.0g，32.86mmol）在甲醇（100mL）中搅拌并浓缩（98％）硫酸（3.0mL）。 将混合物加热至回流18小时。 将反应冷却并浓缩。 将残余物用水（100mL）稀释，并用乙酸乙酯（3×50mL）萃取。 合并的萃取液用无水硫酸镁干燥，过滤并浓缩，得到标题化合物，为橙色油状物，5.46g，100％。 MS M ++ 1 167.通过1H NMR光谱确认结构。
参考文献：
- [1] Patent: WO2004/63184, 2004, A1. Location in patent: Page 53 [2] Patent: US2002/52397, 2002, A1 [3] Patent: US5550152, 1996, A [4] Patent: US5348962, 1994, A
