(3S,4R)-3-[(1R)-1-(tert-butyldimethylsilyloxy)ethyl]-4-[(6R)-2-{(E)-(pyrid-4-yl)methylene}-1-oxocyclohex-6-yl]azetidin-2-one | 208191-56-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: (3S,4R)-3-[(1R)-1-(tert-butyldimethylsilyloxy)ethyl]-4-[(6R)-2-{(E)-(pyrid-4-yl)methylene}-1-oxocyclohex-6-yl]azetidin-2-one
• 英文别名: (3S,4R)-3-[(1R)-1-[tert-butyl(dimethyl)silyl]oxyethyl]-4-[(1R,3E)-2-oxo-3-(pyridin-4-ylmethylidene)cyclohexyl]azetidin-2-one
• CAS: 208191-56-4
• 化学式: C₂₃H₃₄N₂O₃Si
• 分子量: 414.62
• InChiKey: YTZCQIZYNXHWLO-YMASDYJYSA-N

物化性质

• 沸点：
  559.7±50.0 °C(Predicted)
• 密度：
  1.097±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.36
• 重原子数：
  29.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  68.29
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (3S,4R)-3-[(1R)-1-(tert-butyldimethylsilyloxy)ethyl]-4-[(6R)-2-{(E)-(pyrid-4-yl)methylene}-1-oxocyclohex-6-yl]azetidin-2-one 在 碳酸氢钠 作用下， 以 异辛烷 、 二氯甲烷 、 环己烷 、 水 、 甲苯 为溶剂， 反应 2.5h， 生成 9H-fluoren-9-ylmethyl (1S,6E,9aS,9bR)-1-(1-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}ethyl)-2-oxo-6-(4-pyridinylmethylidene)-1,2,6,7,8,9,9a,9b-octahydroazeto[2,1-a]isoindole-4-carboxylate
  参考文献：
  名称：

  The Synthesis of GV143253A: A Case Study for the Use of Analytical and Statistical Tools to Elucidate the Reaction Mechanism and to Optimize the Process

  摘要：

  GV143253A 1 is a broad-spectrum injectable beta-lactam belonging to the class of trinem antibiotics. This article describes the work which enabled a detailed process understanding via several analytical techniques and the subsequent optimization of a key intermediate. By means of a combined application of (31)P NMR spectroscopy and MS spectrometry, the main impurities have been identified and the reaction mechanisms clarified. Moreover, a design of experiments (DoE) approach was applied which substantially improved the overall yield.

  DOI：

  10.1021/op100097c
• 作为产物：
  描述：

  4-乙酰氧基氮杂环丁酮 在 三氟甲磺酸三甲基硅酯 、 碳酸氢钠 作用下， 以 水 、 乙酸乙酯 、 异丙醇 、 乙腈 为溶剂， 反应 4.5h， 生成 (3S,4R)-3-[(1R)-1-(tert-butyldimethylsilyloxy)ethyl]-4-[(6R)-2-{(E)-(pyrid-4-yl)methylene}-1-oxocyclohex-6-yl]azetidin-2-one
  参考文献：
  名称：

  Preparation of the Key Intermediate in the Synthesis of GV143253A:  The Anti-MRSA/E Injectable Trinem

  摘要：

  GV143253A is a broad-spectrum injectable beta-lactam belonging to the class of trinem antibiotics. A key intermediate (3S,4R)-3-[(1R)-1-(tert-butyldimethyl- silyloxy)ethyl]-4-[-(6'R)-2'-[(E)(pyrid-4yl)methylene]-1'-oxocyclohex-6'-yl]azetidin-2-one (10) was identified and synthesized via different enolate coupling approaches, using enol ether, lithium, sodium, magnesium, tin, zinc, zirconium, and titanium enolates. Among these approaches, the synthesis of (3S,4R)-3-[(1R)-1-(tert-butyldimethylsilyloxy)ethyl]-4-[-(6'R)-2'-[(E)-(pyrid-4yl)-methylene]-1'-oxo- cyclohex-6'-yl]azetidin-2-one (10) via a titanium enolate offered advantages in terms of greater diastereoselectivity, higher yield, robustness, and isolation of intermediates and was superior to the method previously used for preparing large quantities of drug substance for early development studies.

  DOI：

  10.1021/op020024l

文献信息

• Preparation of the Key Intermediate in the Synthesis of GV143253A:  The Anti-MRSA/E Injectable Trinem
  作者：Paolo Maragni、Mario Mattioli、Roberta Pachera、Alcide Perboni、Bruno Tamburini

  DOI：10.1021/op020024l

  日期：2002.9.1

  GV143253A is a broad-spectrum injectable beta-lactam belonging to the class of trinem antibiotics. A key intermediate (3S,4R)-3-[(1R)-1-(tert-butyldimethyl- silyloxy)ethyl]-4-[-(6'R)-2'-[(E)(pyrid-4yl)methylene]-1'-oxocyclohex-6'-yl]azetidin-2-one (10) was identified and synthesized via different enolate coupling approaches, using enol ether, lithium, sodium, magnesium, tin, zinc, zirconium, and titanium enolates. Among these approaches, the synthesis of (3S,4R)-3-[(1R)-1-(tert-butyldimethylsilyloxy)ethyl]-4-[-(6'R)-2'-[(E)-(pyrid-4yl)-methylene]-1'-oxo- cyclohex-6'-yl]azetidin-2-one (10) via a titanium enolate offered advantages in terms of greater diastereoselectivity, higher yield, robustness, and isolation of intermediates and was superior to the method previously used for preparing large quantities of drug substance for early development studies.
• The Synthesis of GV143253A: A Case Study for the Use of Analytical and Statistical Tools to Elucidate the Reaction Mechanism and to Optimize the Process
  作者：Giuseppe Guercio、Alcide Perboni、Francesco Tinazzi、Luca Rovatti、Stefano Provera

  DOI：10.1021/op100097c

  日期：2010.7.16

  GV143253A 1 is a broad-spectrum injectable beta-lactam belonging to the class of trinem antibiotics. This article describes the work which enabled a detailed process understanding via several analytical techniques and the subsequent optimization of a key intermediate. By means of a combined application of (31)P NMR spectroscopy and MS spectrometry, the main impurities have been identified and the reaction mechanisms clarified. Moreover, a design of experiments (DoE) approach was applied which substantially improved the overall yield.