ethyl -1-<(1,1-dimethylethyl)dimethylsilyl>-α,α-difluoro-β-hydroxy-4-oxo-2-azetidinepropanoate | 145452-50-2

• 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: ethyl -1-<(1,1-dimethylethyl)dimethylsilyl>-α,α-difluoro-β-hydroxy-4-oxo-2-azetidinepropanoate
• 英文别名: ethyl (S-(R*,R*))-1-[(1,1-dimethylethyl)dimethylsilyl]-α,α-difluoro-β-hydroxy-4-oxo-2-azetidinepropanoate；ethyl (3S)-3-[(2S)-1-[tert-butyl(dimethyl)silyl]-4-oxoazetidin-2-yl]-2,2-difluoro-3-hydroxypropanoate
• CAS: 145452-50-2
• 化学式: C₁₄H₂₅F₂NO₄Si
• 分子量: 337.439
• InChiKey: CSUVJCVUQHCCQZ-ONGXEEELSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.15
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl -1-<(1,1-dimethylethyl)dimethylsilyl>-α,α-difluoro-β-hydroxy-4-oxo-2-azetidinepropanoate 在 戴斯-马丁氧化剂 、 三乙胺 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 17.08h， 生成 -1-<3-<<(1,1-dimethylethyl)dimethylsilyl>oxy>-3-(4-oxo-2-azetidinyl)-2,2-difluoro-3-ethoxy-1-oxopropyl>pyrrolidine
  参考文献：
  名称：

  Synthesis of a peptidyl difluoro ketone bearing the aspartic acid side chain: an inhibitor of interleukin-1.beta. converting enzyme

  摘要：

  The synthesis of the peptidyl difluoro ketone 1, an inhibitor of interleukin-1beta converting enzyme (ICE), was accomplished by a route beginning with the reaction of BrZnCF2CO2Et (2) with (2S)-1-(tert-butyldimethyl-silyl)-4-oxo-2-azetidinecarboxaldehyde (3) to give a mixture of epimeric alcohols 4 and 5. Conversion of alcohol 5 to 1 was carried out by a sequence including the novel coupling of beta-lactam 17 and BOC-Ala-O(succinimide) to form lactone 18. An early attempt to synthesize 1 utilized the beta-lactam ketone 10 obtained in two steps from either 4 or 5. This underwent addition of ethanol and stereoselective migration of the tert-butyldimethylsilyl group to afford the mixed silyl ethyl ketal 12. Unfortunately, efforts to open the beta-lactam ring of 12 and couple the intermediate beta-amino ester 14 to BOC-Ala-O(succinimide) were complicated by an unexpected cyclization reaction. The difluoro ketone 1 was found to exist as a mixture of diastereomeric gamma-hydroxy lactone tautomers in chloroform solution.

  DOI：

  10.1021/jo00052a054
• 作为产物：
  描述：

  二氟溴乙酸乙酯 、 (2S)-1-[(1,1-dimethylethyl)dimethylsilyl]-4-oxo-2-azetidinecarboxaldehyde 在 锌 作用下， 以 四氢呋喃 为溶剂， 反应 40.0h， 以31.5%的产率得到ethyl -1-<(1,1-dimethylethyl)dimethylsilyl>-α,α-difluoro-β-hydroxy-4-oxo-2-azetidinepropanoate
  参考文献：
  名称：

  Synthesis of a peptidyl difluoro ketone bearing the aspartic acid side chain: an inhibitor of interleukin-1.beta. converting enzyme

  摘要：

  The synthesis of the peptidyl difluoro ketone 1, an inhibitor of interleukin-1beta converting enzyme (ICE), was accomplished by a route beginning with the reaction of BrZnCF2CO2Et (2) with (2S)-1-(tert-butyldimethyl-silyl)-4-oxo-2-azetidinecarboxaldehyde (3) to give a mixture of epimeric alcohols 4 and 5. Conversion of alcohol 5 to 1 was carried out by a sequence including the novel coupling of beta-lactam 17 and BOC-Ala-O(succinimide) to form lactone 18. An early attempt to synthesize 1 utilized the beta-lactam ketone 10 obtained in two steps from either 4 or 5. This underwent addition of ethanol and stereoselective migration of the tert-butyldimethylsilyl group to afford the mixed silyl ethyl ketal 12. Unfortunately, efforts to open the beta-lactam ring of 12 and couple the intermediate beta-amino ester 14 to BOC-Ala-O(succinimide) were complicated by an unexpected cyclization reaction. The difluoro ketone 1 was found to exist as a mixture of diastereomeric gamma-hydroxy lactone tautomers in chloroform solution.

  DOI：

  10.1021/jo00052a054

文献信息

• Synthesis of a peptidyl difluoro ketone bearing the aspartic acid side chain: an inhibitor of interleukin-1.beta. converting enzyme
  作者：Ralph P. Robinson、Kathleen M. Donahue

  DOI：10.1021/jo00052a054

  日期：1992.12

  The synthesis of the peptidyl difluoro ketone 1, an inhibitor of interleukin-1beta converting enzyme (ICE), was accomplished by a route beginning with the reaction of BrZnCF2CO2Et (2) with (2S)-1-(tert-butyldimethyl-silyl)-4-oxo-2-azetidinecarboxaldehyde (3) to give a mixture of epimeric alcohols 4 and 5. Conversion of alcohol 5 to 1 was carried out by a sequence including the novel coupling of beta-lactam 17 and BOC-Ala-O(succinimide) to form lactone 18. An early attempt to synthesize 1 utilized the beta-lactam ketone 10 obtained in two steps from either 4 or 5. This underwent addition of ethanol and stereoselective migration of the tert-butyldimethylsilyl group to afford the mixed silyl ethyl ketal 12. Unfortunately, efforts to open the beta-lactam ring of 12 and couple the intermediate beta-amino ester 14 to BOC-Ala-O(succinimide) were complicated by an unexpected cyclization reaction. The difluoro ketone 1 was found to exist as a mixture of diastereomeric gamma-hydroxy lactone tautomers in chloroform solution.