(S)-3-phenyl-3-(4-(trifluoromethyl)phenoxy)propionic acid | 406945-08-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: (S)-3-phenyl-3-(4-(trifluoromethyl)phenoxy)propionic acid
• 英文别名: (3S)-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propanoic acid
• CAS: 406945-08-2
• 化学式: C₁₆H₁₃F₃O₃
• 分子量: 310.273
• InChiKey: QXMMAJMDXZHOET-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (S)-3-phenyl-3-(4-(trifluoromethyl)phenoxy)propionic acid 在 N-甲基吗啉 、 盐酸 、 硼烷 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 28.5h， 生成 (3S)-N-甲基-3-苯基-3-[4-(三氟甲基)苯氧基]-1-丙胺盐酸盐(1:1)
  参考文献：
  名称：

  Enantioselective synthesis of (S)- and (R)-fluoxetine hydrochloride

  摘要：

  The enantioselective synthesis of fluoxetine hydrochloride, a potent serotonin-uptake inhibitor, is described. The synthesis of (S)-fluoxetine hydrochloride begins with the asymmetric carbonyl-ene reaction of benzaldehyde with 3-methylene-2,3-dihydrofuran (1) catalyzed by Ti[OCH(CH3)(2)](4)/(S)-BINOL to give (S)-2-(3-furyl)-1-phenyl-1-ethanol (2) in 90% yield and 95% ee. In five steps, alcohol 2 was converted into (S)-fluoxetine hydrochloride (97% ee and 56% overall yield from benzaldehyde). (R)-fluoxetine hydrochloride was prepared by the same sequence except that Ti[OCH(CH3)(2)](4)/(R)-BINOL was used in the first reaction to give the enantiomer of 2. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(01)01012-2
• 作为产物：
  描述：

  (S)-2-(3-furyl)-1-phenylethyl[1-(trifluoromethyl)phenyl] ether 在 ruthenium trichloride 、 sodium periodate 作用下， 以 水 、 乙酸乙酯 为溶剂， 反应 1.75h， 以85%的产率得到(S)-3-phenyl-3-(4-(trifluoromethyl)phenoxy)propionic acid
  参考文献：
  名称：

  Enantioselective synthesis of (S)- and (R)-fluoxetine hydrochloride

  摘要：

  The enantioselective synthesis of fluoxetine hydrochloride, a potent serotonin-uptake inhibitor, is described. The synthesis of (S)-fluoxetine hydrochloride begins with the asymmetric carbonyl-ene reaction of benzaldehyde with 3-methylene-2,3-dihydrofuran (1) catalyzed by Ti[OCH(CH3)(2)](4)/(S)-BINOL to give (S)-2-(3-furyl)-1-phenyl-1-ethanol (2) in 90% yield and 95% ee. In five steps, alcohol 2 was converted into (S)-fluoxetine hydrochloride (97% ee and 56% overall yield from benzaldehyde). (R)-fluoxetine hydrochloride was prepared by the same sequence except that Ti[OCH(CH3)(2)](4)/(R)-BINOL was used in the first reaction to give the enantiomer of 2. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(01)01012-2

文献信息

• Enantioselective Heck Arylation of Acyclic Alkenol Aryl Ethers: Synthetic Applications and DFT Investigation of the Stereoselectivity
  作者：Ellen Christine Polo、Martí Fernández Wang、Ricardo Almir Angnes、Ataualpa A. C. Braga、Carlos Roque Duarte Correia

  DOI：10.1002/adsc.201901471

  日期：2020.2.21

  Heck‐Matsuda adducts were further converted into more complex and valuable scaffolds including their synthetic application in the synthesis of (R)‐Fluoxetine, (R)‐Atomoxetine, and in the synthesis of an enantioenriched benzo[c]chromene. Finally, in silico mechanistic investigations into the reaction's enantioselectivity were performed using density functional theory.

  在本文中，我们报告了无环E和Z链烯基芳基醚的对映选择性Heck-Matsuda芳基化。反应在温和的条件下进行，以区域选择性的方式得到对映体富集的苄基醚，中等至良好的收率（高达73％），以及良好至优异的对映体比率（高达97：3）。对映体选择性的Heck-松田芳基化已经显示出宽范围（25个实施例），并且一些关键的Heck-松田加合物进一步转化成更复杂的和有价值的支架包括在（合成及其合成应用- [R）-Fluoxetine，（- [R ）-托莫西汀，以及在对映体富集的苯并[ c ]色烯的合成中。最后，在计算机上 使用密度泛函理论对反应的对映选择性进行了机理研究。
• Enantioselective synthesis of (S)- and (R)-fluoxetine hydrochloride
  作者：William H Miles、Elizabeth J Fialcowitz、E Scott Halstead

  DOI：10.1016/s0040-4020(01)01012-2

  日期：2001.12

  The enantioselective synthesis of fluoxetine hydrochloride, a potent serotonin-uptake inhibitor, is described. The synthesis of (S)-fluoxetine hydrochloride begins with the asymmetric carbonyl-ene reaction of benzaldehyde with 3-methylene-2,3-dihydrofuran (1) catalyzed by Ti[OCH(CH3)(2)](4)/(S)-BINOL to give (S)-2-(3-furyl)-1-phenyl-1-ethanol (2) in 90% yield and 95% ee. In five steps, alcohol 2 was converted into (S)-fluoxetine hydrochloride (97% ee and 56% overall yield from benzaldehyde). (R)-fluoxetine hydrochloride was prepared by the same sequence except that Ti[OCH(CH3)(2)](4)/(R)-BINOL was used in the first reaction to give the enantiomer of 2. (C) 2001 Elsevier Science Ltd. All rights reserved.