ethyl -1-<(1,1-dimethylethyl)dimethylsilyl>-α,α-difluoro-β-hydroxy-4-oxo-2-azetidinepropanoate | 145452-51-3

• 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 [R-(R*,S*)]-1-[(1,1-dimethylethyl)dimethylsilyl]-α,α-difluoro-β-hydroxy-4-oxo-2-azetidinepropanoate；ethyl (3R)-3-[(2S)-1-[tert-butyl(dimethyl)silyl]-4-oxoazetidin-2-yl]-2,2-difluoro-3-hydroxypropanoate
• CAS: 145452-51-3
• 化学式: C₁₄H₂₅F₂NO₄Si
• 分子量: 337.439
• InChiKey: CSUVJCVUQHCCQZ-GXSJLCMTSA-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 氢氟酸 作用下， 以 吡啶 、 二氯甲烷 、 乙腈 为溶剂， 反应 3.5h， 生成 -1-<3-(4-oxo-2-azetidinyl)-2,2-difluoro-3-hydroxy-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 以 四氢呋喃 、 正己烷 、 乙酸乙酯 为溶剂， 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：

  Peptidyl 4-amino-2,2-difluoro-3-oxo-1,6-hexanedioic acid derivatives as

  摘要：

  本发明涉及公式（A）的化合物，它们是4-氨基-2,2-二氟-3-氧代-1,6-己二酸的衍生物及其药学上可接受的盐。这些衍生物及其盐对抑制白细胞介素1β转换酶和治疗哺乳动物的炎症状况有用。该发明还声称三个（3）中间体，它们对于制备所述衍生物和盐是有用的。

  公开号：

  US05739279A1

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.
• Peptidyl 4-amino-2,2-difluoro-3-oxo-1,6-hexanedioic acid derivatives as
  申请人：Pfizer Inc.

  公开号：US05739279A1

  公开（公告）日：1998-04-14

  This invention relates to compounds of formula (A) which are derivatives of 4-amino-2,2-difluoro-3-oxo-1,6-hexanedioic acid and their pharmaceutically acceptable base salts. These derivatives and salts thereof are useful for inhibiting interleukin 1.beta. converting enzyme and for treating inflammatory conditions in mammals. The invention also claims three (3) intermediates which are useful for the preparation of said derivatives and salts.

  本发明涉及公式（A）的化合物，它们是4-氨基-2,2-二氟-3-氧代-1,6-己二酸的衍生物及其药学上可接受的盐。这些衍生物及其盐对抑制白细胞介素1β转换酶和治疗哺乳动物的炎症状况有用。该发明还声称三个（3）中间体，它们对于制备所述衍生物和盐是有用的。