1,6-二氧杂螺[2.5]辛烷在医药和农药领域有应用,具体用途未详细说明。
医药; 农药
合成路线 1(1. 合成:185-72-8)
产率:63%
合成条件:Stage #1: With sodium hydride In dimethyl sulfoxide; mineral oil at 20℃; for 1 h; Inert atmosphere Stage #2: at 20℃; for 1 h;
实验步骤:在氮气氛下将碘化三甲基氧化锍(286mg,13mmol)溶解于DMSO(20mL)中。 然后分批加入NaH(60%在矿物油中的分散体,520mg,13mmol)(观察到NB。剧烈的泡腾)。 将所得悬浮液在室温下搅拌1小时,随后滴加四氢-4H-吡喃-4-酮1-107(0.93mL,10mmol)。 将反应混合物在室温下再搅拌1小时,然后将其倒入水/冰浆液中。 水相用Et.20(x3)萃取,合并的有机萃取液用水和盐水洗涤,然后用MgSO 4干燥。 真空浓缩,得到标题化合物,为浅黄色油状物(725mg,6.3mmol,63%)。
参考文献:
- [1] ChemMedChem, 2010, vol. 5, # 1, p. 65 - 78 [2] Patent: WO2017/93543, 2017, A2. Location in patent: Page/Page column 114 [3] Patent: TWI609011, 2017, B. Location in patent: Page/Page column 68; 69 [4] Patent: EP2680844, 2016, B1. Location in patent: Paragraph 0128 [5] Patent: TW2018/8946, 2018, A. Location in patent: Page/Page column 59
合成路线 2(2. 合成:185-72-8)
产率:52%
合成条件:With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 0 - 20℃; for 3 h;
实验步骤:实施例H8:4-r((2-β5S)-44f3-r(5-氟-2-甲基嘧啶-4-基)氨基-6,6-二甲基-β-二氢吡咯并吡唑-SdHWIlcarbonvD ^。δ-二甲基哌嗪-1-基)methyl1tetrahvdro-2H-吡喃-4-醇; 中间体H8(i):1,6-二氧杂螺[2.5]辛烷; 将4-亚甲基四氢-2H-吡喃(1.00g,10.2mmol)的CH 2 Cl 2(30mL)溶液置于冰浴中,然后分三份加入甲氧基 - 氯过氧苯甲酸(2.46g,14.3mmol)。 将反应缓慢温热至室温并搅拌3小时,然后用10%NaOH(aq)(10mL)淬灭,并用CH 2 Cl 2(2×15mL)萃取。 将合并的萃取液干燥(MgSO 4),过滤并浓缩,得到中间体H8(i),为透明油状物(607mg,52%)。
参考文献:
- [1] Patent: WO2008/96260, 2008, A1. Location in patent: Page/Page column 62 [2] Patent: WO2008/125945, 2008, A2. Location in patent: Page/Page column 43 [3] Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation), 1982, vol. 31, p. 1866 - 1873 [4] Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1982, # 9, p. 2114 - 2121 [5] Chemistry of Heterocyclic Compounds, 1997, vol. 33, # 7, p. 778 - 782
合成路线 3(3. 合成:185-72-8)
产率:59%
合成条件:With sodium hydride In tetrahydrofuran; dimethyl sulfoxide; mineral oil at 0 - 20℃; for 18 h; Inert atmosphere
实验步骤:在氮气下,将6.6g氢化钠(60%在矿物油中)悬浮在90ml四氢呋喃中并冷却至0℃.91.7分批加入三甲基碘化锍。 向该混合物中滴加15g二氢-2H-吡喃-4(3H) - 酮在300ml二甲基亚砜和60ml四氢呋喃中的溶液。 然后将混合物温热至室温并搅拌18小时。 然后将混合物倒入1.2升冰水中并用二乙醚萃取三次。 将合并的有机相用盐水洗涤并用硫酸钠干燥。 真空蒸发溶剂得到产物。产量:10.15g(理论值的59%)Rf值:0.47(硅胶,石油醚/乙酸乙酯1:1)
参考文献:
- [1] Patent: US2012/46304, 2012, A1. Location in patent: Page/Page column 178 [2] Patent: WO2013/24130, 2013, A1. Location in patent: Page/Page column 46; 47 [3] Patent: US2013/210850, 2013, A1. Location in patent: Paragraph 0269-0272 [4] Patent: WO2017/173358, 2017, A1. Location in patent: Paragraph 00136 [5] Patent: US2011/28492, 2011, A1. Location in patent: Page/Page column 24 [6] Patent: WO2011/26904, 2011, A1. Location in patent: Page/Page column 63-64 [7] Patent: WO2012/66065, 2012, A1. Location in patent: Page/Page column 83 [8] Patent: WO2012/66070, 2012, A1. Location in patent: Page/Page column 90 [9] Patent: WO2012/101065, 2012, A2. Location in patent: Page/Page column 86-87 [10] Patent: WO2012/101063, 2012, A1. Location in patent: Page/Page column 120 [11] Patent: WO2012/101066, 2012, A1. Location in patent: Page/Page column 73; 97 [12] Patent: WO2012/101064, 2012, A1. Location in patent: Page/Page column 161