作为有机合成中间体，用于医药、农药等领域的相关化合物合成。
医药; 农药
合成路线 1（1. 合成：39977-44-1）
产率：92%
合成条件：With sodium tetrahydroborate In methanol; dichloromethane at 0 - 20℃;
实验步骤：向100mL圆底烧瓶中加入2,6-二甲基吡啶-2,6-二羧酸酯（950mg，4.87mmol，1.00当量）在甲醇（33.2mL）的溶剂混合物中的溶液。 和二氯甲烷（14.2mL）。 在0℃下分几批将NaB（185mg，5.02mmol，1.00当量）加入到反应混合物中。 将所得溶液在室温下搅拌过夜，然后通过加入50mL NC1（aq。）淬灭。 所得溶液用2×50mL二氯甲烷萃取，合并的有机层用无水硫酸钠干燥并真空浓缩。 将残余物加到硅胶柱上，用乙酸乙酯/石油醚（1：1-2：1）作为洗脱剂，得到750mg（92％）6-（羟甲基）吡啶-2-羧酸甲酯，为白色固体。
参考文献：
- [1] Patent: WO2013/102145, 2013, A1. Location in patent: Paragraph 0333 [2] Patent: US2015/344483, 2015, A1. Location in patent: Paragraph 0616; 0617 [3] Chemistry - A European Journal, 2017, vol. 23, # 21, p. 5154 - 5170 [4] Chemistry - A European Journal, 2006, vol. 12, # 24, p. 6393 - 6402 [5] Bioorganic and Medicinal Chemistry Letters, 2003, vol. 13, # 4, p. 609 - 612 [6] Patent: WO2004/37808, 2004, A1. Location in patent: Page 9-10 [7] Chemistry - A European Journal, 2015, vol. 21, # 28, p. 10179 - 10184 [8] Patent: US2005/131017, 2005, A1. Location in patent: Page/Page column 106 [9] Inorganic Chemistry, 2013, vol. 52, # 11, p. 6346 - 6353 [10] Inorganic Chemistry, 2013, vol. 52, # 20, p. 11956 - 11965 [11] Tetrahedron, 2015, vol. 71, # 33, p. 5321 - 5336 [12] Angewandte Chemie, International Edition, 2009, vol. 48, # 40, p. 7383 - 7386 [13] Angewandte Chemie, 2009, vol. 121, # 40, p. 7519 - 7522 [14] Patent: US2006/19965, 2006, A1. Location in patent: Page/Page column 24 [15] Tetrahedron Letters, 2010, vol. 51, # 51, p. 6707 - 6710 [16] Patent: CN106496110, 2017, A. Location in patent: Paragraph 0009; 0024; 0025; 0026 [17] Zeitschrift fur Anorganische und Allgemeine Chemie, 2018, vol. 644, # 14, p. 719 - 728 [18] Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy, 2005, vol. 61, # 6, p. 1089 - 1096 [19] Molecules, 2017, vol. 22, # 5, [20] Organic and Biomolecular Chemistry, 2015, vol. 13, # 37, p. 9551 - 9558 [21] Inorganic Chemistry, 2015, vol. 54, # 10, p. 4909 - 4926 [22] Tetrahedron Letters, 2013, vol. 54, # 10, p. 1236 - 1238 [23] Carbohydrate Research, 2013, vol. 372, p. 35 - 46 [24] European Journal of Organic Chemistry, 2018, vol. 2018, # 40, p. 5489 - 5498 [25] Chemistry of Heterocyclic Compounds, 2009, vol. 45, # 2, p. 161 - 168 [26] Chinese Journal of Chemistry, 2016, vol. 34, # 8, p. 757 - 762 [27] Chemistry - A European Journal, 2013, vol. 19, # 45, p. 15346 - 15357 [28] Patent: US2014/187527, 2014, A1. Location in patent: Paragraph 0140 [29] Journal of Organic Chemistry, 2017, vol. 82, # 12, p. 6082 - 6088 [30] Polyhedron, 2013, vol. 52, p. 1336 - 1343 [31] Synthetic Communications, 2007, vol. 37, # 19, p. 3393 - 3402 [32] Inorganic Chemistry, 2013, vol. 52, # 7, p. 4084 - 4096 [33] Journal of Medicinal Chemistry, 2006, vol. 49, # 8, p. 2628 - 2639 [34] Chemistry - A European Journal, 2004, vol. 10, # 14, p. 3579 - 3590 [35] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 19, p. 5330 - 5335 [36] Journal of the American Chemical Society, 2009, vol. 131, p. 3331 - 3341 [37] Patent: US2004/204455, 2004, A1. Location in patent: Page/Page column 19 [38] Inorganic Chemistry, 2011, vol. 50, # 11, p. 4987 - 4999 [39] Inorganic Chemistry, 2012, vol. 51, # 12, p. 6916 - 6927 [40] Dalton Transactions, 2013, vol. 42, # 42, p. 15113 - 15119 [41] Chemical Communications, 2013, vol. 49, # 91, p. 10739 - 10741 [42] European Journal of Inorganic Chemistry, 2014, # 25, p. 4159 - 4167,9 [43] European Journal of Inorganic Chemistry, 2014, vol. 2014, # 25, p. 4159 - 4167 [44] Chemistry - A European Journal, 2016, vol. 22, # 51, p. 18532 - 18550 [45] Inorganic Chemistry, 2016, vol. 55, # 24, p. 12544 - 12558 [46] Patent: CN104926720, 2018, B. Location in patent: Paragraph 0038; 0039; 0041; 0043; 0044
合成路线 2（2. 合成：39977-44-1）
产率：54%
合成条件：Stage #1: With sodium tetrahydroborate In methanol; dichloromethane at -40 - 20℃; Stage #2: With hydrogenchloride In methanol; dichloromethane; water for 0.33 h;
实验步骤：向2-甲基吡啶-2,6-二甲酸-2-甲基酯（3.0g，14,3mmol）的MeOH（20mL）溶液和CH 2 Cl 2（10mL）中缓慢加入NaBH 4（1.95g，51.6mmol）。 几个部分在-40°C。 10分钟后，将反应混合物在室温下搅拌1小时。 向反应混合物中加入5mL 1N HCl并将混合物搅拌20分钟。 真空除去溶剂，残余物用CHCl 3和饱和NaHCO 3水溶液（20mL）稀释。 分离有机层，经MgSO 4干燥，过滤，将滤液真空浓缩，得到所需化合物（2.6g，54％），为白色固体。 1H NMR（DMSO-d）<58.02（t，J = 8.0Hz，1H），7.92（4J = SO Hz，1H），7.73（d，J = 8.0Hz，1H），4.62（d，J = 8.0Hz，2H），3.88（s，3H）。 MS（ESI）：168.1（M + H）+。
参考文献：
- [1] Patent: WO2009/152082, 2009, A1. Location in patent: Page/Page column 213
