化学合成;作为有机中间体和医药中间体,用于实验室研发过程和化工医药分析过程中;可通过水解4-甲基-1,3-噁唑-5-甲酸乙酯制备,经NaOH水解、树脂交换等步骤得到产物。
有机中间体;医药中间体
路线1:
- 步骤:将2-氯乙酰乙酸乙酯(1重量;1当量,1000克)用甲酰胺(0.68体积;约2.8当量)老化,加热至120℃反应5小时;冷却至室温,氮气下老化过夜;用NaOH(3M,6体积,反应适度放热)处理,室温搅拌4小时;加入乙酸乙酯(6体积),分离各相,弃去有机层,用浓盐酸水溶液(32%)调pH至2.0(约2.0体积),沉淀开始形成;用AcOEt(8体积)处理悬浮液并搅拌至大部分沉淀物溶解;水相用AcOEt进一步萃取两次(每次6体积),合并有机层蒸馏至低体积;加入新鲜AcOEt(8体积),蒸发至干;收集固体在减压下40℃烘箱放置过夜,得到4-甲基-1,3-恶唑-5-羧酸(498g,64.5%)。
- 条件:Stage #1: 120℃,5小时;Stage #2: 20℃,4小时(NaOH处理及搅拌阶段);
- 收率:64.5%;
- 参考文献:[1] Patent: WO2005/80382, 2005, A1. Location in patent: Page/Page column 47-48;[2] Patent: WO2007/22933, 2007, A1. Location in patent: Page/Page column 31-32;[3] Patent: WO2007/22980, 2007, A1. Location in patent: Page/Page column 35; 36;[4] Patent: WO2005/123717, 2005, A1. Location in patent: Page/Page column 21-22;[5] Patent: WO2006/108700, 2006, A1. Location in patent: Page/Page column 34-35;[6] Patent: WO2016/67043, 2016, A1. Location in patent: Page/Page column 108;[7] Patent: WO2017/21920, 2017, A1. Location in patent: Paragraph 0495; 0496;[8] Patent: US2018/297990, 2018, A1. Location in patent: Paragraph 0227;[9] Patent: WO2007/22980, 2007, A1. Location in patent: Page/Page column 131;[10] Patent: WO2008/22994, 2008, A1. Location in patent: Page/Page column 18