(R)-(+)-4-chloro-1-(4-fluorophenyl)butan-1-ol | 126640-11-7

• 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: (R)-(+)-4-chloro-1-(4-fluorophenyl)butan-1-ol
• 英文别名: (1R)-4-chloro-1-(4-fluorophenyl)butan-1-ol
• CAS: 126640-11-7
• 化学式: C₁₀H₁₂ClFO
• 分子量: 202.656
• InChiKey: YTEUQGXRCFYPSA-SNVBAGLBSA-N

物化性质

• 沸点：
  301.0±37.0 °C(Predicted)
• 密度：
  1.198±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  20.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (R)-(+)-4-chloro-1-(4-fluorophenyl)butan-1-ol 在 4-二甲氨基吡啶 、 碳酸氢钠 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 (1R)-(+)-4-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]-1-(4-fluorophenyl)butyl 4-phenylbutanoate
  参考文献：
  名称：

  Haloperidol metabolite II prodrug: Asymmetric synthesis and biological evaluation on rat C6 glioma cells

  摘要：

  In a previous work we reported the antiproliferative effects of (+/-)-MRJF4, a novel haloperidol metabolite II (HP-mII) (a sigma-1 antagonist and sigma-2 agonist) prodrug, obtained through conjugation to 4-phenylbutyric acid (PhBA) [a histone deacetylase inhibitor (HDACi)] via an ester bond. As a continuation of this work, here we report the asymmetric synthesis of compounds (R)-(+)-MRJF4 and (S)(-)-MRJF4 and the evaluation of their biological activity on rat C6 glioma cells, derived from glioblastoma multiforme (GBM), which is the most common and deadliest central nervous system (CNS) invasive malignancy. Favourable physicochemical properties, high permeability in the parallel artificial membrane permeability assay (PAMPA), good enzymatic and chemical stability, in vivo anticancer activity, associated with the capacity to reduce cell viability and to increase cell death by apoptosis, render compound (R)-(+)-MRJF4 a promising candidate for the development of a useful therapeutic for gliomas therapy. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.11.012
• 作为产物：
  描述：

  [(1R)-4-chloro-1-(4-fluorophenyl)butyl] acetate 在 potassium carbonate 作用下， 以 甲醇 为溶剂， 反应 4.0h， 生成 (R)-(+)-4-chloro-1-(4-fluorophenyl)butan-1-ol
  参考文献：
  名称：

  化学酶法合成（R）-（+）- α-（4-氟苯基）-4-（2-嘧啶基）-1-哌嗪丁醇和（R）-（+）- α-（4-氟苯基）-4-甲基-1-哌啶丁醇作为潜在的抗精神病药

  摘要：

  化学酶法直接合成（R） -（+）-α-（4-氟苯基）-4-甲基-1-哌啶丁醇（2）和（R）-（+）- α-（4-氟苯基）-4- （2-嘧啶基）-1-哌嗪丁醇（3），两种潜在的抗精神病药，已通过两种不同的方法开发，涉及脂肪酶介导的外消旋化合物的拆分或通过前体醇4的不对称化。第二次酶解，然后将（R）-4与4-甲基哌啶（6）或1-（2-嘧啶基）哌嗪（7）缩合，得到的（R）-2和（R）-3具有良好的化学性质和优异的光学收率（> 99％ee）。

  DOI：

  10.1016/s0040-4020(97)10009-6

文献信息

• A convenient enantioselective CBS-reduction of arylketones in flow-microreactor systems
  作者：Sonia De Angelis、Maddalena De Renzo、Claudia Carlucci、Leonardo Degennaro、Renzo Luisi

  DOI：10.1039/c6ob00336b

  日期：——

  A convenient, versatile, and green CBS-asymmetric reduction of aryl and heteroaryl ketones has been developed by using the microreactor technology.

  一种便捷、多用途且环保的CBS不对称还原芳基和杂芳基酮的方法已经通过使用微反应器技术得以开发。
• Cobalt-catalyzed asymmetric hydroboration of aryl ketones with pinacolborane
  作者：Jun Guo、Jianhui Chen、Zhan Lu

  DOI：10.1039/c5cc01084e

  日期：——

  The highly enantioselective cobalt-catalyzed hydroboration reaction of aryl ketones with HBpin was developed using iminopyridine oxazoline ligands. Halides, amines, ethers, sulfides, esters and amides are well tolerated under the mild reaction conditions, demonstrating its synthetic advantage. Substituted diaryl ketones could also be hydroborated with high enantioselectivity.

  使用亚氨基吡啶恶唑啉配体开发了芳基酮与HBpin的高对映选择性钴催化的硼氢化反应。在温和的反应条件下，卤化物，胺，醚，硫化物，酯和酰胺具有良好的耐受性，证明了其合成优势。取代的二芳基酮也可以高对映选择性进行硼氢化。
• Iminophenyl Oxazolinylphenylamine for Enantioselective Cobalt-Catalyzed Hydrosilylation of Aryl Ketones
  作者：Xu Chen、Zhan Lu

  DOI：10.1021/acs.orglett.6b02260

  日期：2016.9.16

  synthesized through three steps from commercially available starting materials. An efficient cobalt-catalyzed asymmetric hydrosilylation of simple ketones with a low catalyst loading of CoCl2 and IPOPA was developed to afford chiral alcohols in good yields with high enantioselectivities.

  从市售原料中分三步设计并合成了一个新的手性亚氨基苯基恶唑啉基苯基胺家族（IPOPA）。开发了有效的钴催化的简单酮的低负载CoCl 2和IPOPA的钴的不对称氢化硅烷化反应，以高收率和高对映选择性提供手性醇。
• Novel phenylheteroalkylamine derivatives
  申请人：——

  公开号：US20030105161A1

  公开（公告）日：2003-06-05

  There are provided novel compounds of formula (I), 1 wherein R 1 , R 2 , X, Y, V, W and Z are as defined in the specification, and pharmaceutically acceptable salts thereof, and enantiomers and racemates thereof; together with processes for their preparation, compositions containing them and their use in therapy. The compounds are inhibitors of nitric oxide synthase and are thereby particularly useful in the treatment or prophylaxis of inflammatory disease and pain.

  提供了式（I）的新化合物， 其中R1、R2、X、Y、V、W和Z如规范中所定义，并且其药学上可接受的盐，以及其对映体和消旋体；以及它们的制备方法，含有它们的组合物以及它们在治疗中的用途。这些化合物是一氧化氮合酶的抑制剂，因此在治疗或预防炎症性疾病和疼痛方面特别有用。
• Copper(ii)-catalyzed enantioselective hydrosilylation of halo-substituted alkyl aryl and heteroaryl ketones: asymmetric synthesis of (R)-fluoxetine and (S)-duloxetine
  作者：Ji-Ning Zhou、Qiang Fang、Yi-Hu Hu、Li-Yao Yang、Fei-Fei Wu、Lin-Jie Xie、Jing Wu、Shijun Li

  DOI：10.1039/c3ob42214c

  日期：——

  copper-catalyzed enantioselective hydrosilylation of a number of structurally diverse β-, γ- or ε-halo-substituted alkyl aryl ketones and α-, β- or γ-halo-substituted alkyl heteroaryl ketones under air to afford a broad spectrum of halo alcohols in high yields and good to excellent enantioselectivities (up to 99% ee). The developed procedure has been successfully applied to the asymmetric synthesis of antidepressant

  已经建立了一套反应条件，以促进多种结构上不同的β-，γ-或ε-卤代烷基芳基酮和α-，β-或γ-卤代-的非贵金属铜催化的对映选择性氢化硅烷化。在空气中被取代的烷基杂芳基酮，以高收率提供良好范围的卤代醇，并具有良好至优异的对映选择性（高达99％ee）。所开发的方法已成功地用于抗抑郁药（R）-氟西汀和（S）-度洛西汀的不对称合成，突出了其合成实用性。