(3S,4R)-1-benzyl-4-(4-fluorophenyl)-2,6-dioxopiperidine-3-carboxylic acid methyl ester | 511284-07-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (3S,4R)-1-benzyl-4-(4-fluorophenyl)-2,6-dioxopiperidine-3-carboxylic acid methyl ester
• 英文别名: (3S,4R)-3-methoxycarbonyl-4-(4-fluorophenyl)-N-benzylpiperidine-2,6-dione；methyl (3S,4R)-1-benzyl-4-(4-fluorophenyl)-2,6-dioxopiperidine-3-carboxylate
• CAS: 511284-07-4
• 化学式: C₂₀H₁₈FNO₄
• 分子量: 355.366
• InChiKey: MZZAXJZWWKCLSG-WMZOPIPTSA-N

物化性质

• 沸点：
  536.7±50.0 °C(Predicted)
• 密度：
  1.293±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  63.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3S,4R)-1-benzyl-4-(4-fluorophenyl)-2,6-dioxopiperidine-3-carboxylic acid methyl ester 在 吡啶 、 lithium aluminium tetrahydride 、 1-chloroethyl formate 、 sodium methylate 作用下， 以 四氢呋喃 、 甲醇 、 1,2-二氯乙烷 为溶剂， 反应 6.0h， 生成 帕罗西汀
  参考文献：
  名称：

  Application of the chiral base desymmetrisation of imides to the synthesis of the alkaloid jamtine and the antidepressant paroxetine

  摘要：

  The synthesis of the alkaloid jamtine and the antidepressant paroxetine have been addressed by a strategy involving asymmetric desymmetrisation of prochiral imides by a chiral lithium amide base. A short reaction sequence, starting with a cyclohexane fused succinimide, led to the structures originally reported for the alkaloid jamine and its derived N-oxide. The structures synthesised are shown not to correspond with those originally reported. A second sequence involves desymmetrisation of a 4-arylglutarimide, and provides a short enantioselective synthesis of the drug substance paroxetine. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2003.08.046
• 作为产物：
  描述：

  氰基甲酸甲酯 、 1-(phenylmethyl)-4-(4-fluorophenyl)piperidin-2,6-dione 在 (R,S,S,R)-PhCH(Me)N(Li)CH(Ph)CH(Ph)N(Li)CH(Me)Ph 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 3.75h， 以71%的产率得到(3S,4R)-1-benzyl-4-(4-fluorophenyl)-2,6-dioxopiperidine-3-carboxylic acid methyl ester
  参考文献：
  名称：

  A Novel Chiral Base Mediated Glutarimide Desymmetrisation: Application to the Asymmetric Synthesis of (-)-Paroxetine

  摘要：

  某些4-芳基取代戊二酰亚胺的不对称去对称化反应通过与手性双锂酰胺碱的烯醇化作用，实现了高水平的对映选择性（高达97% ee）。反应的选择性被证明是由不对称烯醇化引起的，随后进行了动力学拆分。合成的一种手性亚胺被转化为选择性血清素再摄取抑制剂（-）-帕罗西汀。

  DOI：

  10.1055/s-2002-35588

文献信息

• Catalytic Michael/Ring-Closure Reaction of α,β-Unsaturated Pyrazoleamides with Amidomalonates: Asymmetric Synthesis of (−)-Paroxetine
  作者：Yu Zhang、Yuting Liao、Xiaohua Liu、Qian Yao、Yuhang Zhou、Lili Lin、Xiaoming Feng

  DOI：10.1002/chem.201603056

  日期：2016.10.10

  A highly enantioselective tandem Michael/ring‐closure reaction of α,β‐unsaturated pyrazoleamides and amidomalonates has been accomplished in the presence of a chiral N,N′‐dioxide–Yb(OTf)3 complex (Tf: trifluoromethanesulfonyl) to give various substituted chiral glutarimides with high yields and diastereo‐ and enantioselectivities. Moreover, this methodology could be used for gram‐scale manipulation

  在手性N，N′-二氧化物-Yb （OTf）3配合物（Tf：三氟甲磺酰基）存在下，完成了对映体串联的α，β-不饱和吡唑酰胺和酰胺基丙酸酯的迈克尔/环封闭反应，得到各种取代基手性戊二酰亚胺，收率高，非对映和对映选择性高。此外，该方法可用于克级处理，并已成功应用于（-）-帕罗西汀的合成。进一步非线性和HRMS的研究显示，实际催化活性物质是一种单体大号-PMe 2 -Yb 3+络合物。提出了一个合理的过渡态来解释不对称感应的起源。
• Application of the chiral base desymmetrisation of imides to the synthesis of the alkaloid jamtine and the antidepressant paroxetine
  作者：Christopher D Gill、Daniel A Greenhalgh、Nigel S Simpkins

  DOI：10.1016/j.tet.2003.08.046

  日期：2003.11

  The synthesis of the alkaloid jamtine and the antidepressant paroxetine have been addressed by a strategy involving asymmetric desymmetrisation of prochiral imides by a chiral lithium amide base. A short reaction sequence, starting with a cyclohexane fused succinimide, led to the structures originally reported for the alkaloid jamine and its derived N-oxide. The structures synthesised are shown not to correspond with those originally reported. A second sequence involves desymmetrisation of a 4-arylglutarimide, and provides a short enantioselective synthesis of the drug substance paroxetine. (C) 2003 Elsevier Ltd. All rights reserved.
• A Novel Chiral Base Mediated Glutarimide Desymmetrisation: Application to the Asymmetric Synthesis of (-)-Paroxetine
  作者：Nigel S. Simpkins、Daniel A. Greenhalgh

  DOI：10.1055/s-2002-35588

  日期：——

  The asymmetric desymmetrisation of certain 4-aryl substituted glutarimides has been accomplished with high levels of selectivity (up to 97% ee) by enolisation with a chiral bis-lithium amide base. The selectivity of the reaction is shown to be the result of asymmetric enolisation, followed by a kinetic resolution. One of the chiral imides synthesised was converted into the selective seratonin reuptake inhibitor (-)-paroxetine.

  某些4-芳基取代戊二酰亚胺的不对称去对称化反应通过与手性双锂酰胺碱的烯醇化作用，实现了高水平的对映选择性（高达97% ee）。反应的选择性被证明是由不对称烯醇化引起的，随后进行了动力学拆分。合成的一种手性亚胺被转化为选择性血清素再摄取抑制剂（-）-帕罗西汀。