化学合成。
化学合成
合成路线 1（1. 合成：337915-79-4）
产率：93%
合成条件：With zinc In methanol; water at 20℃; for 1 h;
实验步骤：将12a（350mg，1.51mmol），锌（495mg，7.57mmol）和NH 4 Cl（810mg，15.15mmol）在MeOH（4mL）/水（2mL）中的溶液在室温下搅拌1小时。 通过过滤除去不溶物质并中和饱和NaHCO 3溶液。 浓缩混合物并用EtOAc萃取。 分离有机层，用水和盐水洗涤，经MgSO 4干燥，真空浓缩，得到标题化合物，为棕色固体（282mg，93％）。 1H NMR（400MHz，DMSO-d6）δ2.68（3H，d，J = 4.9Hz），4.60（2H，s），4.87（1H，d，J = 4.9Hz），6.32-6.58（3H，m）。 MS（ESI / APCI）m / z = 202.09 [M + H] +。
参考文献：
- [1] Bioorganic and Medicinal Chemistry, 2016, vol. 24, # 11, p. 2486 - 2503 [2] Patent: CN108689942, 2018, A. Location in patent: Paragraph 0463; 0468-0469 [3] Patent: WO2012/174312, 2012, A2. Location in patent: Page/Page column 216-217 [4] Patent: WO2008/82487, 2008, A2. Location in patent: Page/Page column 111-112 [5] Patent: WO2004/111036, 2004, A1. Location in patent: Page 21 [6] Patent: WO2004/111046, 2004, A2. Location in patent: Page/Page column 18-19 [7] Patent: US2010/113461, 2010, A1. Location in patent: Page/Page column 17 [8] Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 6, p. 1939 - 1943 [9] Patent: WO2008/12623, 2008, A1. Location in patent: Page/Page column 60-61 [10] Patent: WO2011/12622, 2011, A1. Location in patent: Page/Page column 68 [11] Patent: WO2011/109277, 2011, A1. Location in patent: Page/Page column 30-31 [12] Patent: WO2012/21382, 2012, A1. Location in patent: Page/Page column 30 [13] Patent: US2012/108578, 2012, A1. Location in patent: Page/Page column 27 [14] Patent: WO2013/105676, 2013, A1. Location in patent: Page/Page column 143; 144 [15] Patent: WO2014/100734, 2014, A1. Location in patent: Paragraph 00319 [16] Patent: WO2015/200677, 2015, A2. Location in patent: Paragraph 00457; 00458 [17] Patent: WO2016/57834, 2016, A1. Location in patent: Paragraph 000800 [18] Patent: WO2017/69980, 2017, A1. Location in patent: Paragraph 00418 [19] Patent: WO2017/176960, 2017, A1. Location in patent: Paragraph 00748 [20] Patent: WO2007/135527, 2007, A2. Location in patent: Page/Page column 66
合成路线 2（2. 合成：337915-79-4）
产率：96%
合成条件：With platinum on activated charcoal; hydrogen In ethyl acetate at 20℃; for 4 h;
实验步骤：向I-36.1（5.27g，22.81mmol）的乙酸乙酯溶液中加入铂（550mg）并在氢气（5巴）下于室温下搅拌。 持续4小时。 将反应混合物通过硅藻土垫过滤并浓缩。 粗产物无需进一步纯化即可用于下一步骤。 产量96％。
参考文献：
- [1] Patent: US2014/275025, 2014, A1. Location in patent: Paragraph 0618; 0626
