ethyl 1-fluoro-2-methylenecyclopropane-1-carboxylate | 862578-72-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: ethyl 1-fluoro-2-methylenecyclopropane-1-carboxylate
• 英文别名: Cyclopropanecarboxylic acid, 1-fluoro-2-methylene-, ethyl ester；ethyl 1-fluoro-2-methylidenecyclopropane-1-carboxylate
• CAS: 862578-72-1
• 化学式: C₇H₉FO₂
• 分子量: 144.146
• InChiKey: QTSHRYQSPATDCN-UHFFFAOYSA-N

物化性质

• 沸点：
  125.7±40.0 °C(Predicted)
• 密度：
  1.10±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  10
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 1-fluoro-2-methylenecyclopropane-1-carboxylate 在 吡啶 、 N-溴代丁二酰亚胺(NBS) 、 二异丁基氢化铝 、 potassium carbonate 作用下， 以 正己烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 55.08h， 生成 (E)-2-amino-6-chloro-9-[(2-acetoxymethyl-2-fluoro-1-phenylselenyl)-1-cyclopropylmethyl]purine
  参考文献：
  名称：

  A new alkylation–elimination method for synthesis of antiviral fluoromethylenecyclopropane analogues of nucleosides

  摘要：

  A new method for the synthesis of fluoromethylenecyclopropane nucleosides by alkylation-elimination procedure is described. Fluorination of methylenecyclopropane carboxylate 6 gave fluoroester 7. Treatment of 7 with phenylselenenyl bromide afforded the desired ethyl (E)-2-bromomethyl-1-fluoro-2-phenylselenenylcyclopropane-1-carboxylate 11 in 85% yield. DIBALH reduction of 11 gave 13, which after acetylation to 14 was reacted with 2-amino-6-chloropurine to give the 9-alkylated product 15 in 87% yield. Se-oxidation of 15 with hydrogen peroxide afforded 16, which underwent smooth elimination in a mixture of THF-DMF at 60 degrees C giving rise to a Z,E mixture of protected nucleosides 17. Deacetylation gave Z-1a and E-1a which were separated on a silica gel column. Both Z-1a and E-la were converted into the respective guanine analogues Z-1b and E-1b. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2005.05.054
• 作为产物：
  描述：

  2-methylene-cyclopropanecarboxylic acid ethyl ester 在 lithium chloride 、 lithium diisopropyl amide 、 N-氟代双苯磺酰胺 作用下， 以 四氢呋喃 为溶剂， 反应 1.01h， 以62%的产率得到ethyl 1-fluoro-2-methylenecyclopropane-1-carboxylate
  参考文献：
  名称：

  A new alkylation–elimination method for synthesis of antiviral fluoromethylenecyclopropane analogues of nucleosides

  摘要：

  A new method for the synthesis of fluoromethylenecyclopropane nucleosides by alkylation-elimination procedure is described. Fluorination of methylenecyclopropane carboxylate 6 gave fluoroester 7. Treatment of 7 with phenylselenenyl bromide afforded the desired ethyl (E)-2-bromomethyl-1-fluoro-2-phenylselenenylcyclopropane-1-carboxylate 11 in 85% yield. DIBALH reduction of 11 gave 13, which after acetylation to 14 was reacted with 2-amino-6-chloropurine to give the 9-alkylated product 15 in 87% yield. Se-oxidation of 15 with hydrogen peroxide afforded 16, which underwent smooth elimination in a mixture of THF-DMF at 60 degrees C giving rise to a Z,E mixture of protected nucleosides 17. Deacetylation gave Z-1a and E-1a which were separated on a silica gel column. Both Z-1a and E-la were converted into the respective guanine analogues Z-1b and E-1b. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2005.05.054

文献信息

• A new alkylation–elimination method for synthesis of antiviral fluoromethylenecyclopropane analogues of nucleosides
  作者：Shaoman Zhou、Jiri Zemlicka

  DOI：10.1016/j.tet.2005.05.054

  日期：2005.7

  A new method for the synthesis of fluoromethylenecyclopropane nucleosides by alkylation-elimination procedure is described. Fluorination of methylenecyclopropane carboxylate 6 gave fluoroester 7. Treatment of 7 with phenylselenenyl bromide afforded the desired ethyl (E)-2-bromomethyl-1-fluoro-2-phenylselenenylcyclopropane-1-carboxylate 11 in 85% yield. DIBALH reduction of 11 gave 13, which after acetylation to 14 was reacted with 2-amino-6-chloropurine to give the 9-alkylated product 15 in 87% yield. Se-oxidation of 15 with hydrogen peroxide afforded 16, which underwent smooth elimination in a mixture of THF-DMF at 60 degrees C giving rise to a Z,E mixture of protected nucleosides 17. Deacetylation gave Z-1a and E-1a which were separated on a silica gel column. Both Z-1a and E-la were converted into the respective guanine analogues Z-1b and E-1b. (c) 2005 Elsevier Ltd. All rights reserved.