四氢-4-氧代-2H-噻喃-3-甲酸甲酯为羧酸酯类衍生物,可用作有机中间体。制备方法:将3,3'-硫代二丙酸二甲酯和NaH(60%)加入至装有四氢呋喃的烧瓶中,室温搅拌反应后,加入水,用二氯甲烷萃取,有机相干燥后减压回收溶剂得目标产物。
有机中间体
合成路线 1(1. 合成:4160-61-6)
- 步骤:将2.7098g NaH(60%)加入干燥的三颈250ml烧瓶中,加入40ml无水四氢呋喃(THF),室温搅拌10min;缓慢滴加3,3'-硫代二丙酸二甲酯(10.1015g)的THF溶液,滴加完毕后继续回流1小时;冷却至室温,用2%盐酸稀释至pH6-7,二氯甲烷(30ml×3)萃取,合并有机层用饱和氯化钠洗涤,无水硫酸钠干燥,减压除溶剂得黄色油状液体。
- 条件:With sodium hydride In tetrahydrofuran for 2 h; Reflux
- 产率:88.7%
- 参考文献:[1] Synthesis, 2007, #10, p.1584-1586;[2] Patent: CN104086562, 2016;[3] Patent: CN105153190, 2017;[4] Organic Letters, 2018, vol.20, #19, p.6104-6107;[5] Journal of the American Chemical Society, 1997, vol.119, #18, p.4285-4291;[6] Journal of Organic Chemistry, 1995, vol.60, #6, p.1665-1673;[7] Chemistry Letters, 1995, #4, p.295-296;[8] Journal of Organic Chemistry, 1995, vol.60, #19, p.6198-6201;[9] Pakistan Journal of Scientific and Industrial Research, 2001, vol.44, #2, p.63-66;[10] Tetrahedron, 1991, vol.47, #27, p.4847-4860;[11] Gazzetta Chimica Italiana, 1959, vol.89, p.1298,1304;[12] Gazzetta Chimica Italiana, 1959, vol.89, p.1127,1136;[13] Journal of the American Chemical Society, 1948, vol.70, p.1813,1816;[14] Acta Chimica Academiae Scientiarum Hungaricae, 1955, vol.5, p.187,194;[15] Gazzetta Chimica Italiana, 1959, vol.89, p.1298,1304;[16] Gazzetta Chimica Italiana, 1959, vol.89, p.1127,1136;[17] Journal of the American Chemical Society, 1948, vol.70, p.1813,1816;[18] Journal of Organic Chemistry, 2002, vol.67, #5, p.1618-1629;[19] Patent: EP1142881, 2001, A1;[20] Patent: WO2009/49018, 2009, A1;[21] Synlett, 2011, #4, p.508-512;[22] Bioorganic and Medicinal Chemistry Letters, 2011, vol.21, #7, p.1942-1947;[23] Bioorganic and Medicinal Chemistry Letters, 2012, vol.22, #15, p.5114-5117;[24] Bioorganic and Medicinal Chemistry, 2014, vol.22, #24, p.6746-6754;[25] European Journal of Medicinal Chemistry, 2016, vol.116, p.27-35;[26] Bioorganic and Medicinal Chemistry, 2016, vol.24, #16, p.3862-3869;[27] Research on Chemical Intermediates, 2017, vol.43, #12, p.7291-7306
合成路线 2(2. 合成:4160-61-6)
- 步骤:将丙烯酸甲酯在乙醚中的溶液冷却至0℃,缓慢加入3-巯基丙酸酯;加入氢化钠,室温搅拌8小时;反应后用水洗涤,无水硫酸镁干燥,减压除溶剂,柱色谱(正己烷:乙酸乙酯=10:1)纯化得目标化合物。
- 条件:at 0 - 20℃; for 8 h;
- 产率:52%
- 参考文献:[1] Canadian Journal of Chemistry, 1982, vol.60, p.437-439;[2] Patent: WO2009/61131, 2009, A2;[3] Tetrahedron Letters, 1989, vol.30, #45, p.6129-6132