化学合成。
化学合成
合成路线 1(1. 合成:21080-80-8)
产率:93%
合成条件:With sodium In ethanol at 0 - 80℃; Inert atmosphere
实验步骤:在室温和氮气氛下将金属钠溶解在EtOH(150ml)溶液中以形成NaOEt(16.19g)。 将该混合物冷却至0℃。 逐滴加入草酸二乙酯(34.76g)和异丙基甲基酮(20gm)约15分钟并温热至室温。 现在加入EtOH(100ml)并在室温下搅拌约1小时。 将该反应混合物加热至80℃约45分钟并冷却至室温并减压浓缩。 为此产生的固体,添加EtOAC。 用EtOH洗涤,在布上过滤,得到细粉末。将该固体溶于水中,用稀硫酸(pH-2)酸化。 该化合物用乙醚萃取,用硫酸钠干燥,减压浓缩,得到棕色液体化合物(40g,收率93%)。
参考文献:
- [1] Patent: WO2010/127855, 2010, A1. Location in patent: Page/Page column 159 [2] Patent: US2012/115903, 2012, A1. Location in patent: Page/Page column 40 [3] Patent: WO2012/62463, 2012, A1. Location in patent: Page/Page column 87-88 [4] Patent: WO2013/39988, 2013, A1. Location in patent: Page/Page column 138 [5] Patent: US2003/236287, 2003, A1. Location in patent: Page 46, 47 [6] Journal of Medicinal Chemistry, 2014, vol. 57, # 11, p. 4720 - 4744 [7] Patent: WO2013/104561, 2013, A1. Location in patent: Page/Page column 48 [8] Patent: WO2010/127856, 2010, A1. Location in patent: Page/Page column 123 [9] Patent: US2012/46301, 2012, A1. Location in patent: Page/Page column 33 [10] Patent: WO2013/13815, 2013, A1. Location in patent: Page/Page column 111 [11] Patent: US2013/29962, 2013, A1. Location in patent: Paragraph 0693 [12] Patent: WO2013/68463, 2013, A1. Location in patent: Page/Page column 51 [13] Patent: WO2013/68461, 2013, A1. Location in patent: Page/Page column 72 [14] Patent: WO2013/68464, 2013, A1. Location in patent: Page/Page column 53 [15] Patent: WO2013/68462, 2013, A1. Location in patent: Page/Page column 61 [16] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 17, p. 4914 - 4919 [17] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 20, p. 5620 - 5623 [18] Journal of Combinatorial Chemistry, 2010, vol. 12, # 4, p. 510 - 517 [19] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 2, p. 714 - 733 [20] Patent: WO2012/62462, 2012, A1. Location in patent: Page/Page column 87 [21] Patent: WO2016/40502, 2016, A1. Location in patent: Page/Page column 64 [22] Patent: WO2016/40504, 2016, A1. Location in patent: Paragraph 0192 [23] Patent: WO2016/40498, 2016, A1. Location in patent: Paragraph 0264 [24] Patent: WO2016/40511, 2016, A1. Location in patent: Paragraph 0114 [25] Patent: WO2016/40515, 2016, A1. Location in patent: Paragraph 0265 [26] Chemical Papers, 2017, vol. 71, # 11, p. 2053 - 2061 [27] Journal of Medicinal Chemistry, 2018,