52085-14-0 4-苯甲氧基-2-羟基苯甲醛

危险性质：非危险化学品

化学合成。

化学合成

合成路线 1（1. 合成：52085-14-0）

产率：100% 合成条件：Stage #1: With sodium hydrogencarbonate In acetonitrile at 20℃; for 0.75 h; Inert atmosphere Stage #2: Inert atmosphere; Reflux 实验步骤：将2,4-二羟基苯甲醛（3.0g，1.0当量）溶解在乙腈（220ml）中，并在室温下用NaHCO 3（2.2当量）处理45分钟，然后加入苄基溴（1.1当量）。 将反应混合物在回流下搅拌。 然后用H 2 O（100ml）淬灭，用乙酸乙酯（3×25ml）萃取。 将合并的有机层用盐水（2×15ml）洗涤，用Na 2 SO 4干燥，过滤并在真空下除去溶剂，得到标题化合物12，为白色固体，其原样使用。 参考文献：

• [1] Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 15, p. 4502 - 4510 [2] Synlett, 2011, # 11, p. 1605 - 1607 [3] Organic Process Research and Development, 2011, vol. 15, # 5, p. 1149 - 1162 [4] Tetrahedron Letters, 2013, vol. 54, # 31, p. 4121 - 4124 [5] Organic Letters, 2008, vol. 10, # 21, p. 5007 - 5010 [6] Patent: US2011/144195, 2011, A1. Location in patent: Page/Page column 2; 4; 11 [7] Phosphorus, Sulfur and Silicon and the Related Elements, 2018, vol. 193, # 5, p. 306 - 316 [8] Phosphorus, Sulfur and Silicon and the Related Elements, 2018, vol. 193, # 9, p. 574 - 581 [9] Journal of Medicinal Chemistry, 2012, vol. 55, # 12, p. 5797 - 5812 [10] Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 15, p. 3633 - 3637 [11] European Journal of Medicinal Chemistry, 2018, vol. 143, p. 1428 - 1435 [12] Patent: WO2015/200514, 2015, A2. Location in patent: Page/Page column 69 [13] Journal of Heterocyclic Chemistry, 1987, vol. 24, # 1, p. 75 - 77 [14] Patent: WO2013/119985, 2013, A1. Location in patent: Paragraph 00335; 00336 [15] Patent: WO2018/83171, 2018, A1. Location in patent: Page/Page column 48; 49 [16] Journal of the American Chemical Society, 2010, vol. 132, # 26, p. 8828 - 8830 [17] Patent: WO2011/94560, 2011, A1. Location in patent: Page/Page column 54 [18] Patent: US9075014, 2015, B2. Location in patent: Page/Page column 39 [19] Patent: WO2012/11125, 2012, A1. Location in patent: Page/Page column 145-146 [20] Rikagaku Kenkyusho Iho, 1940, vol. 19, p. 802,803 [21] Chem.Abstr., 1940, p. 5842 [22] Bioorganic and Medicinal Chemistry Letters, 1997, vol. 7, # 11, p. 1421 - 1426 [23] Patent: US6610687, 2003, B1 [24] Tetrahedron Asymmetry, 2008, vol. 19, # 3, p. 343 - 347 [25] Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 19, p. 5252 - 5254 [26] Journal of Natural Products, 2009, vol. 72, # 11, p. 2072 - 2075 [27] Organic Letters, 2012, vol. 14, # 17, p. 4544 - 4547 [28] Tetrahedron Letters, 2015, vol. 56, # 11, p. 1338 - 1343

合成路线 2（2. 合成：52085-14-0）

产率：77.8% 合成条件：With sodium hydrogencarbonate; potassium iodide In acetonitrile at 60 - 65℃; 实验步骤：一般步骤：将2,4-二羟基苯甲醛（1.38g，0.01mol），取代的苄基氯（0.011mol），NaHCO3（1.26g，0.015mol）和催化量的碘化钾在20mL乙腈中的混合物加热至60° C保持36小时并热过滤，将滤液冷却至10℃并过滤，收集滤饼并用EtOH重结晶，得到化合物10a-g。 参考文献：

• [1] Heterocycles, 2010, vol. 81, # 7, p. 1697 - 1702 [2] Journal of the American Chemical Society, 2006, vol. 128, # 17, p. 5887 - 5894 [3] Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 22, p. 6758 - 6763 [4] Organic and Biomolecular Chemistry, 2017, vol. 15, # 44, p. 9415 - 9423 [5] European Journal of Medicinal Chemistry, 2014, vol. 86, p. 257 - 269 [6] Archiv der Pharmazie, 2014, vol. 347, # 12, p. 936 - 949 [7] Bioorganic and Medicinal Chemistry, 2009, vol. 17, # 18, p. 6567 - 6582 [8] European Journal of Medicinal Chemistry, 2012, vol. 54, p. 879 - 886 [9] Patent: CN104230845, 2017, B. Location in patent: Paragraph 0437; 0438; 0439; 0440 [10] Journal of Organic Chemistry, 2007, vol. 72, # 26, p. 10283 - 10286 [11] Medicinal Chemistry Research, 2016, vol. 25, # 11, p. 2485 - 2497 [12] Patent: CN104478836, 2017, B. Location in patent: Paragraph 0054-0055 [13] Patent: EP1362844, 2003, A1. Location in patent: Page/Page column 131-135 [14] Journal of Medicinal Chemistry, 2012, vol. 55, # 4, p. 1538 - 1552 [15] Synthetic Communications, 1981, vol. 11, # 10, p. 853 - 858 [16] Helvetica Chimica Acta, 1935, vol. 18, p. 816,826 [17] Journal of the American Chemical Society, 1961, vol. 83, p. 4787 - 4792 [18] Patent: US2003/153599, 2003, A1

合成路线 3（3. 合成：52085-14-0）

产率：72% 合成条件：With zinc(II) chloride In 1,2-dichloro-ethane at 80℃; 实验步骤：一般程序：向干净的，烘箱干燥的2英寸螺旋盖小瓶中加入ZnCl 2（1.05当量）和DCE（1mL）。 通过注射器加入邻位保护的苯酚（0.15mmol，1当量）在DCE（0.5mL）中的溶液，并在指定的温度下搅拌反应直至通过TLC分析测定的原料消耗。 然后将反应混合物用饱和NH 4 Cl水溶液（20mL）稀释，分离各层，水相用CH 2 Cl 2（3×10mL）萃取。 将合并的有机级分用饱和NaCl水溶液（20mL）洗涤，干燥（MgSO 4），并减压浓缩。 通过快速色谱法纯化得到的粗物质，用己烷/ EtOAc洗脱，得到邻 - 脱保护的苯酚33mg（72％），为白色固体。 参考文献：

• [1] Acta Chemica Scandinavica, Series B: Organic Chemistry and Biochemistry, 1986, vol. 40, # 5, p. 400 - 401 [2] Chemical and Pharmaceutical Bulletin, 1998, vol. 46, # 2, p. 222 - 230 [3] Tetrahedron Letters, 2012, vol. 53, # 40, p. 5376 - 5379