21911-84-2 3-(苯基氨基)丙酸甲酯

路线1：离子液体稳定的磁性钴纳米颗粒催化合成

• 产率：94%
• 条件：以离子液体[bmim]BF₄稳定的磁性钴纳米颗粒为催化剂，无溶剂，20℃反应0.75小时
• 步骤：在5mol%（0.1mmol）稳定化钴纳米颗粒存在下，搅拌1mmol胺或硫醇与1mmol活化α,β-不饱和化合物（迈克尔受体）；TLC监测反应完成后，加入二氯甲烷，磁场回收催化剂，倾析反应混合物，蒸发溶剂得粗品；硅胶柱色谱纯化（乙酸乙酯/石油醚为洗脱剂）；产物经¹H NMR、¹³C NMR和质谱分析表征
• 参考文献：[1] Synthetic Communications, 2009, vol. 39, # 6, p. 1109 - 1119 [2] RSC Advances, 2016, vol. 6, # 98, p. 95951 - 95956 [3] Monatshefte fur Chemie, 2008, vol. 139, # 9, p. 1041 - 1047 [4] Inorganic Chemistry Communications, 2015, vol. 53, p. 92 - 96 [5] Tetrahedron, 2013, vol. 69, # 6, p. 1712 - 1716 [6] Tetrahedron, 2010, vol. 66, # 5, p. 1091 - 1097 [7] Catalysis Letters, 2018, vol. 148, # 9, p. 2918 - 2928 [8] Asian Journal of Chemistry, 2011, vol. 23, # 9, p. 3792 - 3794 [9] Comptes Rendus Chimie, 2011, vol. 14, # 12, p. 1059 - 1064 [10] Monatshefte fur Chemie, 2012, vol. 143, # 1, p. 109 - 112 [11] Tetrahedron Letters, 2006, vol. 47, # 13, p. 2125 - 2127 [12] Journal of the Chinese Chemical Society, 2010, vol. 57, # 6, p. 1221 - 1226 [13] Journal of the Iranian Chemical Society, 2011, vol. 8, # 3, p. 775 - 781 [14] Indian Journal of Heterocyclic Chemistry, 2010, vol. 20, # 2, p. 169 - 170 [15] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2005, vol. 44, # 4, p. 838 - 841 [16] Tetrahedron Letters, 2016, vol. 57, # 46, p. 5026 - 5032 [17] RSC Advances, 2015, vol. 5, # 51, p. 40950 - 40952 [18] Tetrahedron Letters, 2006, vol. 47, # 48, p. 8583 - 8586 [19] Synthesis, 2008, # 24, p. 3931 - 3936 [20] Organic Process Research and Development, 2008, vol. 12, # 6, p. 1078 - 1088 [21] Synthetic Communications, 2013, vol. 43, # 2, p. 191 - 197,7 [22] Organic Process Research and Development, 2008, vol. 12, # 1, p. 41 - 57 [23] Organic Preparations and Procedures International, 2013, vol. 45, # 1, p. 28 - 43 [24] Synthetic Communications, 2010, vol. 40, # 19, p. 2830 - 2836 [25] Journal of Organic Chemistry, 2016, vol. 81, # 10, p. 4048 - 4057 [26] Organic Letters, 2016, vol. 18, # 23, p. 6140 - 6143 [27] Journal of Organometallic Chemistry, 2003, vol. 665, # 1-2, p. 250 - 257 [28] Tetrahedron, 2010, vol. 66, # 29, p. 5373 - 5377 [29] Synlett, 1998, # 9, p. 975 - 976 [30] Chemical Communications, 2010, vol. 46, # 43, p. 8234 - 8236 [31] Journal of Organic Chemistry, 2009, vol. 74, # 16, p. 6260 - 6265 [32] Tetrahedron, 2004, vol. 60, # 2, p. 383 - 387 [33] Tetrahedron, 2006, vol. 62, # 4, p. 672 - 677 [34] Tetrahedron, 2007, vol. 63, # 4, p. 904 - 909 [35] Patent: US2008/9482, 2008, A1. Location in patent: Page/Page column 121 [36] Research on Chemical Intermediates, 2011, vol. 37, # 8, p. 883 - 890 [37] Journal of the American Chemical Society, 1949, vol. 71, p. 2532,2537 [38] Journal of the American Chemical Society, 1949, vol. 71, p. 1901,1905 [39] , 1967, vol. 3, p. 520 - 526 [40] Zhurnal Organicheskoi Khimii, 1967, vol. 3, p. 542 - 550 [41] Synthesis, 1981, # 5, p. 375 - 376 [42] European Journal of Medicinal Chemistry, 1993, vol. 28, # 11, p. 837 - 852 [43] Journal of the American Chemical Society, 2006, vol. 128, # 5, p. 1446 - 1447 [44] Tetrahedron, 2007, vol. 63, # 29, p. 6764 - 6773 [45] Tetrahedron Letters, 2007, vol. 48, # 49, p. 8735 - 8738 [46] Organic and Biomolecular Chemistry, 2009, vol. 7, # 11, p. 2452 - 2457 [47] Synlett, 2010, # 3, p. 379 - 382 [48] Tetrahedron Letters, 2010, vol. 51, # 33, p. 4455 - 4458 [49] Comptes Rendus Chimie, 2011, vol. 14, # 11, p. 973 - 977 [50] ACS Catalysis, 2013, vol. 3, # 12, p. 2891 - 2904 [51] Organometallics, 2013, vol. 32, # 23, p. 6986 - 6995 [52] Process Biochemistry, 2016, vol. 51, # 10, p. 1420 - 1433

路线2：乙酸/苯基(2-吡啶基)甲醇催化合成

• 产率：63%
• 条件：以乙酸、苯基(2-吡啶基)甲醇为催化剂，乙腈为溶剂，110℃惰性气氛下反应240小时
• 步骤：将醇1（0.324g，1.75mmol）、硝基苯（17）（0.062g，0.052mL，0.5mmol）、丙烯酸甲酯（0.180mL，2mmol）和冰醋酸（0.006g，0.006mL）溶解于乙腈（1mL）中，110℃加热10天；得到化合物18（Rf=0.19，0.056g，63%），为黄色粘性固体，mp 37-38℃；¹HNMRδ2.64（t，J=6.4Hz，2H，CH₂CO₂Me），3.47（t，J=6.5Hz，2H，CH₂NH），3.70（s，3H，OCH₃），4.01（br s，1H，NH），6.64（d，J=7.6Hz，2H，2-H和6-H），6.73（t，J=7.4Hz，1H，4-H），7.19（t，J=7.5Hz，2H，3-H）；最慢移动部分得到酮3（Rf=0.10，0.260g，95%，表示反应1）
• 参考文献：[1] Tetrahedron, 2011, vol. 67, # 1, p. 167 - 172

路线3：酸性氧化铝催化合成

• 产率：97%
• 条件：100-110℃反应3小时
• 步骤：将胺1（15mmol）和丙烯酸甲酯2（10mmol）加入装有磁棒和回流冷凝器的圆底烧瓶中，室温下加入酸性氧化铝（2g，200mol%）；油浴加热至回流，TLC和GC监测反应；反应完成后冷却至室温，滤纸过滤混合物，乙醚冲洗催化剂；旋转蒸发浓缩滤液，硅胶重力柱色谱纯化单加合物；脂族胺的双加合物副产物用75:25己烷/乙酸乙酯洗脱，单加合物用50:50己烷/乙酸乙酯洗脱；芳族胺的单加合物用80:20己烷/乙酸乙酯洗脱；记录纯化加合物3的产率，IR和NMR光谱表征
• 参考文献：[1] Tetrahedron, 2014, vol. 70, # 14, p. 2449 - 2454 [2] Journal of Organic Chemistry, 2009, vol. 74, # 16, p. 6260 - 6265