化学合成。
医药
合成路线 1（1. 合成：25392-41-0）
产率：91%
合成条件：at 90℃; for 5 h;
实验步骤：一般步骤：将苯酚（1.0mmol），β-酮酯（1.5mmol）和MNESA（0.075g）的混合物在90℃下在圆底烧瓶中搅拌一段时间。 通过TLC确认反应完成后，将反应混合物冷却至室温，并使用外部磁场Some场将催化剂与反应混合物分离。 然后将水加入到反应混合物中，并使用EtOAc（29×10mL）萃取产物。 将合并的有机层用无水Na 2 SO 4干燥，过滤并真空浓缩，得到粗产物。 为了进一步纯化，通过在乙醇中重结晶纯化粗产物，以获得所需的纯度。
参考文献：
- [1] Tetrahedron Letters, 2005, vol. 46, # 36, p. 6119 - 6121 [2] Journal of Organic Chemistry, 2008, vol. 73, # 1, p. 287 - 290 [3] Synthetic Communications, 2008, vol. 38, # 13, p. 2082 - 2088 [4] Journal of Chemical Research, 2008, # 4, p. 232 - 234 [5] Synthetic Communications, 2010, vol. 40, # 22, p. 3358 - 3364 [6] Tetrahedron Letters, 2002, vol. 43, # 50, p. 9195 - 9197 [7] Synthetic Communications, 2004, vol. 34, # 21, p. 3997 - 4003 [8] Tetrahedron Letters, 2006, vol. 47, # 19, p. 3279 - 3281 [9] Catalysis Communications, 2011, vol. 14, # 1, p. 62 - 67 [10] Research on Chemical Intermediates, 2016, vol. 42, # 6, p. 6089 - 6103 [11] Chinese Chemical Letters, 2017, vol. 28, # 1, p. 75 - 82 [12] Heterocycles, 2007, vol. 71, # 3, p. 677 - 682 [13] RSC Advances, 2016, vol. 6, # 24, p. 20269 - 20275 [14] Journal of the Chinese Chemical Society, 2014, vol. 61, # 2, p. 213 - 216 [15] Monatshefte fur Chemie, 2007, vol. 138, # 10, p. 997 - 999 [16] Journal of Materials Chemistry B, 2018, vol. 6, # 17, p. 2547 - 2556 [17] European Journal of Organic Chemistry, 2007, # 26, p. 4301 - 4304 [18] Patent: WO2008/1931, 2008, A2. Location in patent: Page/Page column 86-87 [19] Journal of Medicinal Chemistry, 2012, vol. 55, # 4, p. 1538 - 1552 [20] Patent: EP2698369, 2014, A1. Location in patent: Paragraph 0025; 0067 [21] Patent: US2014/113911, 2014, A1. Location in patent: Paragraph 0066; 0204 [22] Journal of the Iranian Chemical Society, 2017, vol. 14, # 3, p. 655 - 663 [23] MedChemComm, 2014, vol. 5, # 5, p. 650 - 654 [24] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2009, vol. 48, # 1, p. 120 - 123 [25] Bioorganic and Medicinal Chemistry Letters, 2018, vol. 28, # 18, p. 3050 - 3056 [26] Journal of Medicinal Chemistry, 2009, vol. 52, # 21, p. 6685 - 6706 [27] Beilstein Journal of Organic Chemistry, 2013, vol. 9, p. 254 - 259 [28] Chemical Communications, 2016, vol. 52, # 34, p. 5852 - 5855 [29] Patent: WO2012/11125, 2012, A1. Location in patent: Page/Page column 136-137 [30] Antiviral Research, 2015, vol. 118, p. 103 - 109 [31] Molecules, 2013, vol. 18, # 5, p. 6057 - 6091 [32] Chemical Communications, 2016, vol. 52, # 85, p. 12574 - 12577 [33] Patent: CN107089963, 2017, A. Location in patent: Paragraph 0019; 0031; 0032; 0033; 0034 [34] Patent: CN104250239, 2016, B. Location in patent: Paragraph 0289; 0290; 0291 [35] Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 1, p. 358 - 365 [36] Macromolecules, 2013, vol. 46, # 13, p. 5133 - 5140 [37] Farmaco, 1995, vol. 50, # 2, p. 125 - 130 [38] Journal of Medicinal Chemistry, 2013, vol. 56, # 11, p. 4671 - 4690 [39] Synthesis (Germany), 2018, vol. 50, # 4, p. 846 - 852 [40] Synthetic Communications, 2006, vol. 36, # 20, p. 2949 - 2956 [41] Heterocycles, 1995, vol. 41, # 4, p. 647 - 650 [42] Journal of the American Chemical Society, 2012, vol. 134, # 35, p. 14310 - 14313 [43] Patent: WO2006/102958, 2006, A1. Location in patent: Page/Page column 29 [44] Journal of Medicinal Chemistry, 2004, vol. 47, # 27, p. 6792 - 6803 [45] Photochemistry and photobiology, 1993, vol. 58, # 4, p. 486 - 491 [46] Chemical Research in Toxicology, 1999, vol. 12, # 7, p. 555 - 559 [47] Organic Letters, 2005, vol. 7, # 25, p. 5565 - 5568 [48] Tetrahedron, 2007, vol. 63, # 6, p. 1353 - 1359 [49] Journal of Medicinal Chemistry, 2007, vol. 50, # 23, p. 5848 - 5852 [50] Patent: US5362628, 1994, A [51] Patent: US5576424, 1996, A [52] Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 1, p. 272 - 275 [53] Journal of Heterocyclic Chemistry, 2011, vol. 48, # 6, p. 1251 - 1257 [54] Patent: WO2012/111849, 2012, A1. Location in patent: Page/Page column 141-142 [55] European Journal of Medicinal Chemistry, 2013, vol. 62, p. 11 - 19 [56] Patent: US2015/87829, 2015, A1. Location in patent: Paragraph 0239 [57] Patent: WO2015/44073, 2015, A1. Location in patent: Page/Page column 63 [58] Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 23, p. 7448 - 7463 [59] Journal of Enzyme Inhibition and Medicinal Chemistry, 2016, vol. 31, # 5, p. 760 - 772 [60] Patent: CN105566267, 2016, A. Location in patent: Paragraph 0092; 0094; 0095 [61] Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 23, p. 5732 - 5735 [62] Journal of Fluorescence, 2016, vol. 26, # 6, p. 2177 - 2185 [63] Patent: CN105566263, 2016, A. Location in patent: Paragraph 0081-0085 [64] Patent: CN107298686, 2017, A. Location in patent: Paragraph 0087; 0088 [65] New Journal of Chemistry, 2017, vol. 41, # 15, p. 7531 - 7543 [66] Patent: CN105017242, 2018, B. Location in patent: Paragraph 0077-0080
合成路线 2（2. 合成：25392-41-0）
产率：65%
合成条件：With toluene-4-sulfonic acid In toluene at 110℃; for 0.75 h; Dean-Stark
实验步骤：1：向搅拌的间苯二酚（10g，91mmol，1当量）和4-氯甲基乙酰乙酸酯（17g，103mmol，1.14当量）在甲苯（150mL）中的溶液中加入对甲苯磺酸（3.6g，19）。 mmol，0.21当量）。 将溶液与Dean-Stark装置连接，并在110℃下加热回流45分钟。 浓缩反应混合物并通过柱色谱（EtOAC：CH 2 Cl 2 1：9）纯化，得到白色固体1（12g，65％收率）。
参考文献：
- [1] Heterocycles, 2007, vol. 71, # 12, p. 2721 - 2733 [2] Patent: WO2014/74845, 2014, A1. Location in patent: Paragraph 0087 [3] Patent: US2017/172147, 2017, A1. Location in patent: Paragraph 0080
