(R)-(+)-3-ethyl-3-(4-nitrophenyl)piperidine-2,6-dione | 170450-74-5

• 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: (R)-(+)-3-ethyl-3-(4-nitrophenyl)piperidine-2,6-dione
• 英文别名: (R)-2-(4-Nitrophenyl)-2-ethylglutarimide；(R)-nitroglutethimide；2,6-Piperidinedione, 3-ethyl-3-(4-nitrophenyl)-, (3R)-；(3R)-3-ethyl-3-(4-nitrophenyl)piperidine-2,6-dione
• CAS: 170450-74-5
• 化学式: C₁₃H₁₄N₂O₄
• 分子量: 262.265
• InChiKey: ZHPKYOHYUWTINN-CYBMUJFWSA-N

物化性质

• 熔点：
  129-129.5 °C(Solv: ethanol (64-17-5))
• 沸点：
  473.3±45.0 °C(Predicted)
• 密度：
  1.263±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  92
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (R)-(+)-3-ethyl-3-(4-nitrophenyl)piperidine-2,6-dione 在 5%-palladium/activated carbon 、 氢气 作用下， 以 水 、 乙酸乙酯 为溶剂， 以82%的产率得到(R)-(+)-氨鲁米特
  参考文献：
  名称：

  Production of (R)-Aminoglutethimide:  A New Route from 1-Chloro-4-nitrobenzene

  摘要：

  The development of a short, safe and enantioselective route for the preparation of (R)-aminoglutethimide is described, The process was designed for economic large-scale manufacture of the bulk drug substance to acceptable quality standards, to allow clinical evaluation of the single enantiomer over the existing racemate. (R)-Aminoglutethimide was prepared from 1-chloro-4-nitrobenzene using a six-stage synthetic sequence, via chemoresolution of key intermediate racemic 4-cyano-4-(4-nitrophenyl)hexanoic acid using (-)-cinchonidine, The process allowed for preparation of several kilograms of the precursor (R)-nitroglutethimide, to cGMP at pilot-plant scale, along with demonstration of the find hydrogenation step to (R)-amino-glutethimide in the laboratory, This route avoids the problems of hazardous nitration technology, and therefore regio-isomer contamination of the product, associated with other procedures. The resolution chemistry described represents an improvement on literature procedures, Optimisation of the asymmetric Michael addition offers an attractive alternative approach.

  DOI：

  10.1021/op9900075
• 作为产物：
  描述：

  Ethyl 4,5-dioxo-3-phenyloxolane-3-carboxylate 在 palladium on activated charcoal 盐酸 、 ammonium hydroxide 、 sodium hydroxide 、 锂硼氢 、 葡萄糖 、 bakers' yeast 、 硫酸 、 氢气 、 三甲基铝 、 硝酸 、 高碘酸 、 pyridinium chlorochromate 、 锌 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 、 氯仿 为溶剂， 反应 23.17h， 生成 (R)-(+)-3-ethyl-3-(4-nitrophenyl)piperidine-2,6-dione
  参考文献：
  名称：

  Bakers' yeast-mediated synthesis of (R)-aminoglutethimide.

  摘要：

  DOI：

  10.1021/jo00122a064

文献信息

• Resolution of 4-cyano-4-(4-nitrophenyl)hexanoic acid: Synthesis of (R) and (S)-3-(4-aminophenyl)-3-ethylpiperidine-2,6-dione (aminoglutethimide1)
  作者：Osman Achmatowicz、Iwona Malinowska、Barbara Szechner、Jan K. Maurin

  DOI：10.1016/s0040-4020(97)00464-x

  日期：1997.6

  Using (R)- or (S)-1-phenylethylamine as a resolving agent, (R)- and (S)-4-cyano-4-(4-nitrophenyl)hexanoic acids have been isolated. Cyclization of each enantiomer, followed by reduction of the nitro group, afforded (R)- and (S)-aminoglutethimide of high (>99% ee) enantiomeric purity, respectively. The absolute configuration of (R)-(+)-3-(4-nitrophenyl)-3-ethylpiperidine-2, 6-dione was solved by X-ray single crystal analysis thus establishing the (R)-configuration of the dextrorotatory aminoglutethimide. Attempted resolution of the other precursor of aminoglutethimide, 4cyano-2-ethyl(4-nitrophenyl)butanoic acid with (S)-1-phenylethylamine led to the formation of the double salt. Its crystal structure was elucidated by X-ray crystallographic analysis. (C) 1997 Elsevier Science Ltd.
• CHIRAL COMPOUNDS AND THEIR RESOLUTION
  申请人：Chiroscience Limited

  公开号：EP0763023A1

  公开（公告）日：1997-03-19
• [EN] CHIRAL COMPOUNDS AND THEIR RESOLUTION<br/>[FR] COMPOSES CHIRAUX ET LEUR RESOLUTION
  申请人：CHIROSCIENCE LIMITED

  公开号：WO1995032947A1

  公开（公告）日：1995-12-07

  (EN) Enantiomeric glutarimides such as aminoglutethimide and rogletimide are prepared by cyclisation of a corresponding ester-nitrile which is a good substrate for biotransformation with an enantiospecific esterase.(FR) On prépare des glutarimides énantiomères tels que l'aminoglutéthimide et le roglétimide par cyclisation d'un ester-nitrile correspondant constituant un bon substrat pour la biotransformation à l'aide d'une estérase énantiospécifique.
• Production of (<i>R</i>)-Aminoglutethimide:  A New Route from 1-Chloro-4-nitrobenzene
  作者：Michael J. Bunegar、Ulrich C. Dyer、Graham R. Evans、Richard P. Hewitt、Stephen W. Jones、Neil Henderson、Christopher J. Richards、Sivadasan Sivaprasad、Benjamin M. Skead、Mark A. Stark、Eric Teale

  DOI：10.1021/op9900075

  日期：1999.11.1

  The development of a short, safe and enantioselective route for the preparation of (R)-aminoglutethimide is described, The process was designed for economic large-scale manufacture of the bulk drug substance to acceptable quality standards, to allow clinical evaluation of the single enantiomer over the existing racemate. (R)-Aminoglutethimide was prepared from 1-chloro-4-nitrobenzene using a six-stage synthetic sequence, via chemoresolution of key intermediate racemic 4-cyano-4-(4-nitrophenyl)hexanoic acid using (-)-cinchonidine, The process allowed for preparation of several kilograms of the precursor (R)-nitroglutethimide, to cGMP at pilot-plant scale, along with demonstration of the find hydrogenation step to (R)-amino-glutethimide in the laboratory, This route avoids the problems of hazardous nitration technology, and therefore regio-isomer contamination of the product, associated with other procedures. The resolution chemistry described represents an improvement on literature procedures, Optimisation of the asymmetric Michael addition offers an attractive alternative approach.
• Bakers' yeast-mediated synthesis of (R)-aminoglutethimide.
  作者：Giovanni Fogliato、Giovanni Fronza、Claudio Fuganti、Piero Grasselli、Stefano Servi

  DOI：10.1021/jo00122a064

  日期：1995.9