51145-57-4 2-乙酰基-3-(二甲基氨基)丙烯酸乙酯

运输信息：常温运输。危险描述：非危险化学品，危险品运输编号UN2735，危险等级IRRITANT，海关编码2922500090。

路线1：乙酰乙酸乙酯与1,1-二甲氧基-N,N-二甲基甲胺反应

• 步骤：将3-氧代丁酸乙酯（250ml，1961mmol）在室温下搅拌，逐滴加入1,1-二甲氧基-N,N-二甲基甲胺（327ml，2452mmol），室温搅拌过夜；真空浓缩反应混合物，与甲苯（3×300mL）共沸后高真空处理，得到油状物产物，不经纯化直接使用。
• 条件：20℃；
• 收率：100%；
• 参考文献：[1] Patent: WO2006/73361, 2006, A1. Location in patent: Page/Page column 147 [2] Patent: US2007/244088, 2007, A1. Location in patent: Page/Page column 38 [3] Patent: US2008/9523, 2008, A1. Location in patent: Page/Page column 18; 19 [4] Patent: WO2008/4943, 2008, A1. Location in patent: Page/Page column 59 [5] Patent: WO2008/4942, 2008, A1. Location in patent: Page/Page column 56 [6] Patent: WO2009/48765, 2009, A1. Location in patent: Page/Page column 13 [7] Patent: WO2008/141020, 2008, A1. Location in patent: Page/Page column 59 [8] Journal of Labelled Compounds and Radiopharmaceuticals, 2011, vol. 54, # 6, p. 324 - 331 [9] Journal of Molecular Structure, 2019, vol. 1175, p. 551 - 565 [10] RSC Advances, 2017, vol. 7, # 45, p. 28483 - 28488 [11] Journal of Heterocyclic Chemistry, 1987, vol. 24, p. 693 - 695 [12] Tetrahedron Letters, 1998, vol. 39, # 3-4, p. 213 - 216 [13] Journal of Heterocyclic Chemistry, 1987, vol. 24, # 6, p. 1669 - 1675 [14] Chemical Biology and Drug Design, 2018, vol. 92, # 3, p. 1683 - 1691 [15] Patent: US2012/22251, 2012, A1. Location in patent: Page/Page column 27 [16] Patent: EP2602260, 2013, A1. Location in patent: Paragraph 0141 [17] Patent: EP1364949, 2003, A1. Location in patent: Page/Page column 100 [18] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1992, # 20, p. 2603 - 2608 [19] Synthesis, 1990, # 1, p. 70 - 72 [20] Journal of Heterocyclic Chemistry, 1997, vol. 34, # 1, p. 177 - 193 [21] Patent: US5321002, 1994, A [22] Patent: WO2007/8140, 2007, A1. Location in patent: Page/Page column 86 [23] Patent: US2008/176827, 2008, A1. Location in patent: Page/Page column 18 [24] Patent: WO2008/85119, 2008, A1. Location in patent: Page/Page column 103 [25] Patent: US2004/147561, 2004, A1. Location in patent: Page 45 [26] Patent: US2005/20564, 2005, A1. Location in patent: Page/Page column 14 [27] Patent: WO2010/5385, 2010, A1. Location in patent: Page/Page column 77; 85 [28] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 23, p. 6591 - 6594 [29] Patent: US2006/211603, 2006, A1. Location in patent: Page/Page column 80-81 [30] Patent: WO2011/42797, 2011, A1. Location in patent: Page/Page column 69 [31] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 21, p. 6756 - 6761 [32] Organic Process Research and Development, 2012, vol. 16, # 11, p. 1846 - 1853 [33] Organic Process Research and Development, 2012, vol. 16, # 10, p. 1618 - 1625 [34] Organic Process Research and Development, 2013, vol. 17, # 12, p. 1543 - 1551 [35] Research on Chemical Intermediates, 2016, vol. 42, # 3, p. 2597 - 2617 [36] Monatshefte fur Chemie, 2016, vol. 147, # 7, p. 1257 - 1276 [37] Patent: WO2017/176812, 2017, A1. Location in patent: Paragraph 0271 [38] Patent: US2004/220170, 2004, A1. Location in patent: Page 16

路线2：乙酰乙酸乙酯与N,N-二甲基甲酰胺二甲基缩醛在对甲苯磺酸催化下反应

• 步骤：在100mL研磨瓶中依次加入乙酸乙酯（10.00g，78.02mmol）、N,N-二甲基甲酰胺二甲基缩醛（DMFDMA）（13.75g，115.39mmol）、对甲苯磺酸（0.05g，0.29mmol）；常压蒸馏至蒸汽温度达140℃，再升温至180℃减压蒸馏，得到黄色透明液体产物。
• 条件：N,N-二甲基乙酰胺为溶剂；85℃反应2h；
• 收率：90.93%；
• 参考文献：[1] Patent: CN106866680, 2017, A. Location in patent: Paragraph 0017; 0018; 0019; 0020; 0021 [2] Journal of Medicinal Chemistry, 2012, vol. 55, # 20, p. 8948 - 8952,5

路线3：乙酰乙酸乙酯与N,N-二甲基甲酰胺二甲基缩醛回流反应

• 步骤：将乙酰乙酸乙酯（79mL，0.62mol）加入N,N-二甲基甲酰胺二甲基缩醛（100mL，0.68mol）中，加热回流1h；减压蒸馏除去过量缩醛，残余物再次减压蒸馏，得到目标产物。
• 条件：回流反应；减压蒸馏纯化；产物沸点125-130℃（400Pa）；
• 收率：74%；
• 产物表征：1H-NMR（CDCl3）δ：1.33（3H，t，J = 7.1 Hz），2.33（3H，s），3.04（6H，br s），4.23（2H，q，J = 7.1 Hz），7.68（1H，s）；
• 参考文献：[1] Patent: WO2006/73361, 2006, A1. Location in patent: Page/Page column 147 [2] Patent: US2007/244088, 2007, A1. Location in patent: Page/Page column 38 [3] Patent: US2008/9523, 2008, A1. Location in patent: Page/Page column 18; 19 [4] Patent: WO2008/4943, 2008, A1. Location in patent: Page/Page column 59 [5] Patent: WO2008/4942, 2008, A1. Location in patent: Page/Page column 56

路线4：乙酰乙酸乙酯与N,N-二甲基甲酰胺/二甲基硫酸盐加合物反应

• 步骤：乙酰乙酸乙酯与N,N-二甲基甲酰胺/二甲基硫酸盐加合物（DMF/DMS）在三乙胺存在下反应制备目标产物。
• 条件：二氯甲烷为溶剂；20℃反应2h；
• 收率：79%；
• 参考文献：[1] Patent: WO2010/133973, 2010, A1. Location in patent: Page/Page column 27 [2] Journal of Medicinal Chemistry, 2010, vol. 53, # 22, p. 7918 - 7931