(R)-1-chloro-3-(2-methoxyphenoxy)-3-phenylpropane | 114446-49-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (R)-1-chloro-3-(2-methoxyphenoxy)-3-phenylpropane
• 英文别名: -(+)-1-chloro-3-phenyl-3-(2-methoxyphenoxy)propane；(R)-2-(3-Cloro-1-phenylpropoxy)-1-methoxybenzene；1-[(1R)-3-chloro-1-phenylpropoxy]-2-methoxybenzene
• CAS: 114446-49-0
• 化学式: C₁₆H₁₇ClO₂
• 分子量: 276.763
• InChiKey: MAZJWUVQYXBVCU-CQSZACIVSA-N

物化性质

• 熔点：
  59-61 °C
• 沸点：
  180-200 °C(Press: 0.5 Torr)
• 密度：
  1.137±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  18.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (R)-1-chloro-3-(2-methoxyphenoxy)-3-phenylpropane 在 sodium iodide 作用下， 以 四氢呋喃 、 水 、 丙酮 为溶剂， 反应 19.0h， 生成 (R)-nisoxetine
  参考文献：
  名称：

  Synthesis and C-11 labeling of three potent norepinephrine transporter selective ligands ((R)-nisoxetine, lortalamine, and oxaprotiline) for comparative PET studies in baboons

  摘要：

  Three potent antidepressants, (R)-nisoxetine, lortalamine, and oxaprotiline, with high affinity and high selectivity for the norepinephrine transporter (NET) were synthesized and radiolabeled with C-11 via [C-11]methylation. The reference compounds and their corresponding normethyl precursors were synthesized via multi-step synthetic approaches. The radiochemical syntheses were performed by simple alkylation of the corresponding normethyl precursors with no-carrier-added [C-11]CH3I in DMF. After HPLC purification, (R)-[N-(CH3)-C-1]nisoxetine, [C-11]lortalamine, and [1 v C]oxaprotiline were obtained in 63-97% radiochemical yields, whereas (R)-[O-(CH3)-C-11]nisoxetine was obtained in 23-29% radiochemical yields due to substantial formation of the undesired N-[C-11]methylated byproduct (64-70%). These C-11 labeled tracers allowed us to carry out comparative studies of NET in baboons with positron emission tomography (PET) and evaluate their potential as PET tracers for imaging brain NET. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2005.04.062
• 作为产物：
  描述：

  3-氯-1-苯基丙醇 在 吡啶 、 4-二甲氨基吡啶 、 phosphate buffer 、 novozyme 435 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 288.0h， 生成 (R)-1-chloro-3-(2-methoxyphenoxy)-3-phenylpropane
  参考文献：
  名称：

  Chemoenzymatic synthesis of the non-tricyclic antidepressants Fluoxetine, Tomoxetine and Nisoxetine

  摘要：

  使用来自南极念珠菌的脂肪酶B，通过酯交换和水解分别对3-氯-1-苯基丙醇及其相应的丁酸酯——3-氯-1-苯基-1-丙基丁酸酯进行了动力学拆分。得到的立体构建单元（S）-和（R）-3-氯-1-苯基丙醇被转化为抗抑郁药物氟西汀、托莫西汀和尼索西汀的两种对映体。

  DOI：

  10.1039/b000846j

文献信息

• Chiral synthesis via organoboranes. 18. Selective reductions. 43. Diisopinocampheylchloroborane as an excellent chiral reducing reagent for the synthesis of halo alcohols of high enantiomeric purity. A highly enantioselective synthesis of both optical isomers of Tomoxetine, Fluoxetine, and Nisoxetine
  作者：Morris Srebnik、P. V. Ramachandran、Herbert C. Brown

  DOI：10.1021/jo00248a005

  日期：1988.6
• An efficient route to enantiomerically pure antidepressants: tomoxetine, nisoxetine and fluoxetine
  作者：Manfred P. Schneider、Ulrich Goergens

  DOI：10.1016/s0957-4166(00)80257-8

  日期：1992.4

  Both enantiomers (R)- and (S)- 3-chloro- 1-phenyl- 1-propanol can be obtained conveniently by an efficient enzymatic resolution process. They can be converted via enantioconvergent routes into all enantiomers of the important antidepressants (R)- and (S)- Tomoxetine, Fluoxetine and Nisoxetine.
• BROWN, HERBERT C.
  作者：BROWN, HERBERT C.

  DOI：——

  日期：——
• BROWN, H. C.
  作者：BROWN, H. C.

  DOI：——

  日期：——
• Chemoenzymatic synthesis of the non-tricyclic antidepressants Fluoxetine, Tomoxetine and Nisoxetine
  作者：Hui-Ling Liu、Bård Helge Hoff、Thorleif Anthonsen

  DOI：10.1039/b000846j

  日期：——

  3-Chloro-1-phenylpropan-1-ol and the corresponding butanoate, 3-chloro-1-phenyl-1-propyl butanoate, were kinetically resolved using lipase B from Candida antarctica catalysis by transesterification and hydrolysis respectively. The resulting chiral building blocks (S)- and (R)-3-chloro-1-phenylpropanol were converted into both enantiomers of the antidepressant drugs, Fluoxetine, Tomoxetine and Nisoxetine.

  使用来自南极念珠菌的脂肪酶B，通过酯交换和水解分别对3-氯-1-苯基丙醇及其相应的丁酸酯——3-氯-1-苯基-1-丙基丁酸酯进行了动力学拆分。得到的立体构建单元（S）-和（R）-3-氯-1-苯基丙醇被转化为抗抑郁药物氟西汀、托莫西汀和尼索西汀的两种对映体。