ethyl-3-(2,4-difluorophenyl)-3-hydroxypropanoate | 1247454-30-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: ethyl-3-(2,4-difluorophenyl)-3-hydroxypropanoate
• 英文别名: Ethyl 3-(2,4-difluorophenyl)-3-hydroxypropanoate
• CAS: 1247454-30-3
• 化学式: C₁₁H₁₂F₂O₃
• 分子量: 230.211
• InChiKey: OOWADVRTMVEHCR-UHFFFAOYSA-N

物化性质

• 沸点：
  317.6±37.0 °C(Predicted)
• 密度：
  1.265±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl-3-(2,4-difluorophenyl)-3-hydroxypropanoate 在 lithium aluminium tetrahydride 作用下， 以 乙醚 为溶剂， 生成 1-(2,4-difluorophenyl)-1,3-propanediol
  参考文献：
  名称：

  Pradefovir: A Prodrug That Targets Adefovir to the Liver for the Treatment of Hepatitis B

  摘要：

  Adefovir dipivoxil, a marketed drug for the treatment of hepatitis B, is dosed at submaximally efficacious doses because of renal toxicity. In an effort to improve the therapeutic index of adefovir, 1-aryl-1,3-propanyl prodrugs were synthesized with the rationale that this selectively liver-activated prodrug class would enhance liver levels of the active metabolite adefovir diphosphate (ADV-DP) and/or decrease kidney exposure. The lead prodrug (14, MB06866, pradefovir), identified from a variety of in vitro and in vivo assays, exhibited good oral bioavailability (F = 42%, mesylate salt, rat) and rate of prodrug conversion to ADV-DP. Tissue distribution studies in the rat using radiolabeled materials showed that cyclic 1-aryl-1,3-propanyl prodrugs enhance the delivery of adefovir and its metabolites to the liver, with pradefovir exhibiting a 12-fold improvement in the liver/kidney ratio over adefovir dipivoxil.

  DOI：

  10.1021/jm7012216
• 作为产物：
  描述：

  2,4-二氟苯甲醛 、 碘代醋酸乙酯 在 锰 、 copper(l) iodide 、 三氟乙酸 作用下， 以 乙腈 为溶剂， 反应 12.0h， 以92%的产率得到ethyl-3-(2,4-difluorophenyl)-3-hydroxypropanoate
  参考文献：
  名称：

  通过酮和醛的铜催化重组反应获得 β-羟基酯

  摘要：

  用碘乙酸乙酯完成了一种有效且简单的铜催化的酮和醛的 Reformatsky 反应。使用一系列酮和醛（从芳香族到脂肪族、从不饱和到饱和的酮和醛）可实现出色的 β-羟基酯收率。这种实用且方便的转化是在温和的反应条件下使用廉价、容易获得和商业化的原料进行的。

  DOI：

  10.1055/s-0040-1707110

文献信息

• Access to β-Hydroxyl Esters via Copper-Catalyzed Reformatsky Reaction of Ketones and Aldehydes
  作者：Ren Shi Luo、Lu Ouyang、Jian Hua Liao、Yan Ping Xia

  DOI：10.1055/s-0040-1707110

  日期：2020.9

  An efficient and simple Cu-catalyzed Reformatsky reaction of ketones and aldehydes has been accomplished with ethyl iodoacetate. Excellent yields of β-hydroxyl esters were achieved with a range of ketones and aldehydes, which varied from aromatic to aliphatic, unsaturated to saturated ketones and aldehydes. This practical and convenient transformation was conducted with inexpensive, readily available

  用碘乙酸乙酯完成了一种有效且简单的铜催化的酮和醛的 Reformatsky 反应。使用一系列酮和醛（从芳香族到脂肪族、从不饱和到饱和的酮和醛）可实现出色的 β-羟基酯收率。这种实用且方便的转化是在温和的反应条件下使用廉价、容易获得和商业化的原料进行的。
• Pradefovir: A Prodrug That Targets Adefovir to the Liver for the Treatment of Hepatitis B
  作者：K. Raja Reddy、Michael C. Matelich、Bheemarao G. Ugarkar、Jorge E. Gómez-Galeno、Jay DaRe、Kristin Ollis、Zhili Sun、William Craigo、Timothy J. Colby、James M. Fujitaki、Serge H. Boyer、Paul D. van Poelje、Mark D. Erion

  DOI：10.1021/jm7012216

  日期：2008.2.1

  Adefovir dipivoxil, a marketed drug for the treatment of hepatitis B, is dosed at submaximally efficacious doses because of renal toxicity. In an effort to improve the therapeutic index of adefovir, 1-aryl-1,3-propanyl prodrugs were synthesized with the rationale that this selectively liver-activated prodrug class would enhance liver levels of the active metabolite adefovir diphosphate (ADV-DP) and/or decrease kidney exposure. The lead prodrug (14, MB06866, pradefovir), identified from a variety of in vitro and in vivo assays, exhibited good oral bioavailability (F = 42%, mesylate salt, rat) and rate of prodrug conversion to ADV-DP. Tissue distribution studies in the rat using radiolabeled materials showed that cyclic 1-aryl-1,3-propanyl prodrugs enhance the delivery of adefovir and its metabolites to the liver, with pradefovir exhibiting a 12-fold improvement in the liver/kidney ratio over adefovir dipivoxil.