56026-36-9 6-羟甲基烟酸甲酯

运输信息：常温运输。危险描述：非危险化学品，WGK Germany:3，危险等级为IRRITANT，海关编码2933399990，危险性防范说明P305+P351+P338，信号词Warning，危险性描述H319，危险标志GHS07。

化学合成

化学合成

路线1：

• 原料：2,5-吡啶二甲酸甲酯（54; 100.0g，0.51mol）、CaCl₂（227.4g，2.05mol）、THF（1100mL）、EtOH（1200mL）、NaBH₄（48.6g，1.28mol）、饱和NH₄Cl溶液（1.5L）、水（2.0L）、二氯甲烷（3×3.0L）、MgSO₄
• 步骤：将2,5-吡啶二甲酸甲酯、CaCl₂和THF的混合物与EtOH混合，搅拌30分钟；0℃下分批加入NaBH₄；室温搅拌18小时；缓慢加入饱和NH₄Cl溶液和水，二氯甲烷萃取；合并有机相，MgSO₄干燥，减压浓缩
• 条件：0℃分批加NaBH₄，室温搅拌18h
• 收率：96%
• 参考文献：[1] Patent: WO2010/56549, 2010, A1. Location in patent: Page/Page column 103 [2] Journal of Organic Chemistry, 2010, vol. 75, # 3, p. 650 - 659 [3] Inorganic Chemistry, 2015, vol. 54, # 22, p. 10542 - 10558 [4] Patent: US2010/16373, 2010, A1. Location in patent: Page/Page column 16 [5] Patent: US2016/256578, 2016, A1. Location in patent: Paragraph 0124; 0125 [6] Molecules, 2014, vol. 19, # 1, p. 102 - 121 [7] Patent: CN104418811, 2017, B. Location in patent: Paragraph 0234-0236 [8] Russian Journal of Organic Chemistry, 2017, vol. 53, # 7, p. 963 - 970 [9] Zh. Org. Khim., 2017, vol. 53, # 7, p. 951 - 958,8 [10] Angewandte Chemie - International Edition, 2012, vol. 51, # 24, p. 5852 - 5856 [11] Journal of Medicinal Chemistry, 2004, vol. 47, # 21, p. 5230 - 5234 [12] Tetrahedron, 2008, vol. 64, # 37, p. 8963 - 8973 [13] Patent: WO2009/36996, 2009, A2. Location in patent: Page/Page column 85-86 [14] Patent: WO2011/26917, 2011, A1. Location in patent: Page/Page column 107 [15] Patent: WO2011/26904, 2011, A1. Location in patent: Page/Page column 107 [16] Patent: WO2012/101063, 2012, A1. Location in patent: Page/Page column 180 [17] Patent: WO2012/101064, 2012, A1. Location in patent: Page/Page column 223-224 [18] Patent: WO2013/177668, 2013, A1. Location in patent: Page/Page column 60-61 [19] Journal of the American Chemical Society, 2014, vol. 136, # 29, p. 10450 - 10459 [20] Inorganic Chemistry, 2015, vol. 54, # 4, p. 1901 - 1911 [21] Patent: WO2015/74138, 2015, A1. Location in patent: Page/Page column 82; 83 [22] Patent: WO2015/77866, 2015, A1. Location in patent: Page/Page column 48; 49 [23] Patent: US2015/191473, 2015, A1. Location in patent: Paragraph 0185 [24] Journal of the American Chemical Society, 2015, vol. 137, # 35, p. 11222 - 11225 [25] Patent: WO2015/180612, 2015, A1. Location in patent: Page/Page column 75 [26] Patent: WO2016/106628, 2016, A1. Location in patent: Page/Page column 74 [27] Patent: WO2016/109215, 2016, A1. Location in patent: Page/Page column 58 [28] Patent: US2016/221948, 2016, A1. Location in patent: Paragraph 0444-0446 [29] Patent: WO2018/140809, 2018, A1. Location in patent: Paragraph 00409

路线2：

• 原料：6-[(乙酰氧基)甲基]烟酸甲酯（1.5g，7.2mmol）、CH₃OH（7.5ml）、K₂CO₃（0.03g，0.2mmol）、CH₂Cl₂（3×15ml）、NaSO₄
• 步骤：将6-[(乙酰氧基)甲基]烟酸甲酯溶于CH₃OH，加热至40℃溶解；加入K₂CO₃，室温搅拌2小时；CH₂Cl₂萃取；合并有机层，NaSO₄干燥，真空浓缩
• 条件：20-40℃搅拌2h
• 收率：89%
• 参考文献：[1] Patent: US2003/236264, 2003, A1. Location in patent: Page 53 [2] Patent: WO2016/46390, 2016, A1. Location in patent: Page/Page column 78

路线3：

• 原料：5-(甲氧基羰基)-2-甲基吡啶1-氧化物（12g，72mmol）、DCM（50mL）、TFAA（25mL）、饱和NaHCO₃水溶液、EA、硅胶柱色谱（PE/EtOAc=1/1）
• 步骤：0℃下向5-(甲氧基羰基)-2-甲基吡啶1-氧化物的DCM溶液中滴加TFAA；回流搅拌2小时；浓缩；饱和NaHCO₃调节pH至9；EA萃取；硅胶柱色谱纯化
• 条件：0℃滴加TFAA，回流2h，pH=9，PE/EtOAc=1/1柱层析
• 收率：58%
• 参考文献：[1] Patent: WO2014/114185, 2014, A1. Location in patent: Page/Page column 125 [2] Patent: US2014/206681, 2014, A1. Location in patent: Paragraph 0781 [3] Patent: WO2016/106628, 2016, A1. Location in patent: Page/Page column 69; 70