瑞德南特的合成研究
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TQ 317.5

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国家自然科学基金项目(面上项目,重点项目,重大项目)


Synthesis of Preladenant
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    摘要:

    以4-(4’-羟基苯基)-1-乙酰哌嗪(Ⅰ)为原料,经醚化和水解合成了中间体1-(4’-甲氧乙氧苯基)哌嗪(Ⅲ);从2-呋喃甲酸甲酯(Ⅳ)出发,经酰化、闭环和卤代反应合成了具有氮杂稠环结构中间体(Ⅶ);最后,中间体(Ⅲ)和中间体(Ⅶ)经缩合反应合成了瑞德南特。采用FT-IR、1HNMR和ESI-MS对中间体及目标化合物进行了结构确认。采用常规合成方法,六步反应的收率分别为99.0%、95.4%、98.0%、78.9%、86.9%(以Cl计)和52.5%。为了提高反应总产率,采用超声合成对最后一步缩合反应进行了改进。结果表明,在150 W超声条件下,n(中间体2):n(中间体5)=1.2:1,DMSO为溶剂,碳酸钠为缚酸剂,反应温度90 ℃,反应时间1.5 h,缩合反应的收率为85.4%,产率得到了大幅度提高。

    Abstract:

    An intermediate, 1-(4’-methoxyethoxyl phenyl) piperazine (Ⅲ), was synthesized from 1-(4’-hydroxylphenyl)-piperazinyl ethanone (Ⅰ) via etherification and hydrolysis. Another intermediate (Ⅶ) with a nitrogen condensed ring was prepared from methyl furan-2-carboxylate (Ⅳ) by acylation, ring-closure and halogenation. Finally, Preladenant was prepared from the both intermediates by condensation reaction. FT-IR, 1HNMR and ESI-MS were employed to characterize these intermediates and the aim compound. Through common synthetic method, the yields of these 6 steps are 99.0%, 95.4%, 98.0%, 78.9%, 86.9%(calculated by Cl) and 52.5% , respectively. To obtain higher total yield, ultrasonic was used in the last condensation reaction. The results showed that the condensation yield reached 85.4% when the reaction conditions were as follows the ultrasonic power (150W), the molar ration of intermediate 2 to 5 (1.2 : 1), soluent (DMSO), acid-bonding agent (Na2CO3), reaction temperature (90 ℃) and reaction time (1.5 h). The yield of the condensation is greatly increased by ultrasonic method.

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汤艳峰,朱金丽.瑞德南特的合成研究[J].精细化工,2014,31(10):

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  • 收稿日期:2014-05-12
  • 最后修改日期:2014-07-02
  • 录用日期:2014-07-14
  • 在线发布日期: 2014-09-22
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