1-甲基-5-三氟甲基-1H-吡唑-4-羧酸乙酯主要用于医药和农药领域,具体用途未在文献中详细说明。
医药; 农药
路线1:
- 步骤: 将甲基肼(1.2mL,22.7mmol)缓慢加入到浓盐酸的混合物中;在0℃下,加入HCl(1.95mL,23.7mmol)和EtOH(1.9mL),搅拌30分钟;用EtOH(7.7mL)稀释反应混合物;将得到的甲基肼盐酸盐的乙醇溶液缓慢加入到0℃的2-(乙氧基亚甲基)-4,4,4-三氟-3-氧代丁酸乙酯(4.00mL,20.7mmol)的EtOH(58mL)溶液中;使反应混合物缓慢升温至室温,搅拌过夜;将浅黄色溶液真空浓缩,残余物悬浮于水(20mL)中;用饱和NaHCO₃水溶液碱化水相,加入Na₂CO₃(20mL),并用EtOAc(3×30mL)萃取;合并有机层,用盐水(30mL)洗涤,经Na₂SO₄干燥,过滤并真空浓缩;通过柱色谱法(洗脱液:0-50% EtOAc的庚烷)纯化残余物,得到目标产物。
- 条件: 0℃;室温;真空浓缩;柱色谱法(0-50% EtOAc的庚烷)
- 收率: 64%
- 参考文献: [1] Patent: WO2016/51193, 2016, A1. Location in patent: Paragraph 00615; 00616; 00617 [2] Patent: CN104829605, 2018, B. Location in patent: Paragraph 0048-0051
路线2:
- 步骤: 将2-(乙氧基亚甲基)-4,4,4-三氟-3-氧代丁酸乙酯(10g,0.042mol)溶解在乙醇(120ml)中并冷却至0℃;在0℃加入甲基肼(2.11g,0.046mol)(在浓HCl(4ml)-EtOH(4ml)中预搅拌,0℃,30分钟)在EtOH(20ml)中;将得到的溶液在室温下搅拌18小时;蒸发黄色溶液,将残余物悬浮在水中,用碳酸钠溶液(饱和)碱化,用乙酸乙酯(3×30ml)萃取;分离有机层并用盐水(2×30ml)反洗;分离有机层,干燥(Na₂SO₄),过滤并蒸发,得到油状物;将油状物溶于二氯甲烷中,用ISCO Companion(70g硅胶柱,庚烷至乙酸乙酯:庚烷1:1)纯化;合并合适的级分并蒸发,得到无色油状物。
- 条件: 0℃;室温;蒸发;柱色谱法(庚烷至乙酸乙酯:庚烷1:1)
- 收率: 62%
- 参考文献: [1] Patent: WO2008/59370, 2008, A2. Location in patent: Page/Page column 52 [2] Patent: WO2006/90778, 2006, A1. Location in patent: Page/Page column 8-10 [3] Patent: WO2006/90778, 2006, A1. Location in patent: Page/Page column 14 [4] Patent: WO2006/90778, 2006, A1. Location in patent: Page/Page column 15 [5] Patent: WO2006/90778, 2006, A1. Location in patent: Page/Page column 16 [6] Patent: WO2006/90778, 2006, A1. Location in patent: Page/Page column 17 [7] Patent: WO2006/90778, 2006, A1. Location in patent: Page/Page column 11-14 [8] Patent: WO2006/90778, 2006, A1. Location in patent: Page/Page column 22-23 [9] Patent: WO2006/90778, 2006, A1. Location in patent: Page/Page column 22 [10] Patent: WO2006/90778, 2006, A1. Location in patent: Page/Page column 23 [11] Patent: WO2006/90778, 2006, A1. Location in patent: Page/Page column 21-22 [12] Patent: EP2894150, 2015, A1. Location in patent: Paragraph 0043 [13] Patent: WO2015/97658, 2015, A1. Location in patent: Page/Page column 23; 24