4'-氟联苯-4-羧酸乙酯 | 10540-36-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4'-氟联苯-4-羧酸乙酯
• 英文名称: ethyl 4'-fluorobiphenyl-4-carboxylate
• 英文别名: Ethyl 4-(4-fluorophenyl)benzoate
• CAS: 10540-36-0
• 化学式: C₁₅H₁₃FO₂
• 分子量: 244.265
• InChiKey: MRIRSYFQTAWHGY-UHFFFAOYSA-N

物化性质

• 熔点：
  64.6-65.4℃
• 沸点：
  349.6±25.0 °C(Predicted)
• 密度：
  1.145±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2916399090

反应信息

• 作为反应物：
  描述：

  4'-氟联苯-4-羧酸乙酯 在 4-二甲氨基吡啶 、 sodium hydroxide 、 1,2-二氯乙烷 作用下， 以 四氢呋喃 、 甲醇 、 叔丁醇 为溶剂， 反应 24.0h， 生成 4-(4-fluorophenyl)-N-[4-[(2E)-2-(1H-isothiochromen-4-ylidene)hydrazinyl]-3-nitrophenyl]sulfonylbenzamide
  参考文献：
  名称：

  Discovery of a Potent Inhibitor of the Antiapoptotic Protein Bcl-x_L from NMR and Parallel Synthesis

  摘要：

  The antiapoptotic proteins Bcl-x(L) and Bcl-2 play key roles in the maintenance of normal cellular homeostasis. However, their overexpression can lead to oncogenic transformation and is responsible for drug resistance in certain types of cancer. This makes Bcl-x(L) and Bcl-2 attractive targets for the development of potential anticancer agents. Here we describe the structure-based discovery of a potent Bcl-x(L) inhibitor directed at a hydrophobic groove on the surface of the protein. This groove represents the binding site for BH3 peptides from proapoptotic Bcl-2 family members such as Bak and Bad. Application of NMR-based screening yielded an initial biaryl acid with an affinity (K-d) of similar to 300 mu M for the protein. Following the classical "SAR by NMR" approach, a second-site ligand was identified that bound proximal to the first-site ligand in the hydrophobic groove. From NMR-based structural studies and parallel synthesis, a potent ligand was obtained, which binds to Bcl-x(L) with an inhibition constant (K-i) of 36 +/- 2 nM.

  DOI：

  10.1021/jm0507532
• 作为产物：
  描述：

  sodium 4-fluorobenzenesulfinate 在 四(三苯基膦)钯 、 二(三叔丁基膦)钯 、 silver carbonate 作用下， 以 N,N-二甲基乙酰胺 、 甲苯 为溶剂， 反应 9.0h， 生成 4'-氟联苯-4-羧酸乙酯
  参考文献：
  名称：

  钯亚锡与二锡烷的钯催化脱硫偶联反应合成芳基锡烷

  摘要：

  实现了新颖的钯催化的芳基亚磺酸钠与六烷基二锡烷的脱硫交叉偶联反应，从而能够以中等至优异的产率轻松合成官能化的芳基锡烷。克级合成和串联斯蒂勒偶联反应的成功实施证明了该方法在有机合成中的潜在应用。

  DOI：

  10.1016/j.tetlet.2018.09.065

文献信息

• A convenient chemical-microbial method for developing fluorinated pharmaceuticals
  作者：Tara V. Bright、Fay Dalton、Victoria L. Elder、Cormac D. Murphy、Neil K. O'Connor、Graham Sandford

  DOI：10.1039/c2ob27140k

  日期：——

  A significant proportion of pharmaceuticals are fluorinated and selecting the site of fluorine incorporation can be an important beneficial part a drug development process. Here we describe initial experiments aimed at the development of a general method of selecting optimum sites on pro-drug molecules for fluorination, so that metabolic stability may be improved. Several model biphenyl derivatives were transformed by the fungus Cunninghamella elegans and the bacterium Streptomyces griseus, both of which contain cytochromes P450 that mimic oxidation processes in vivo, so that the site of oxidation could be determined. Subsequently, fluorinated biphenyl derivatives were synthesised using appropriate Suzuki–Miyaura coupling reactions, positioning the fluorine atom at the pre-determined site of microbial oxidation; the fluorinated biphenyl derivatives were incubated with the microorganisms and the degree of oxidation assessed. Biphenyl-4-carboxylic acid was transformed completely to 4′-hydroxybiphenyl-4-carboxylic acid by C. elegans but, in contrast, the 4′-fluoro-analogue remained untransformed exemplifying the microbial oxidation – chemical fluorination concept. 2′-Fluoro- and 3′-fluoro-biphenyl-4-carboxylic acid were also transformed, but more slowly than the non-fluorinated biphenyl carboxylic acid derivative. Thus, it is possible to design compounds in an iterative fashion with a longer metabolic half-life by identifying the sites that are most easily oxidised by in vitro methods and subsequent fluorination without recourse to extensive animal studies.

  大部分药物含有氟元素，在药物开发过程中，选择氟元素的加入位置可能是一个有益的环节。在这里，我们描述了初始实验，旨在开发一种通用方法，选择前药分子上最佳的氟化位置，以提高代谢稳定性。通过含有细胞色素P450的真菌和细菌分别对几种联苯衍生物进行转化，这些细胞色素P450模拟了体内的氧化过程，从而确定了氧化位置。随后，利用适当的铃木-宫浦偶联反应合成了氟化联苯衍生物，将氟原子置于预定微生物氧化的位置；这些氟化联苯衍生物与微生物共培养，并评估了氧化程度。结果显示，联苯-4-羧酸被Cunninghamella elegans完全转化为4′-羟基联苯-4-羧酸，但4′-氟代衍生物保持不变，证明了微生物氧化-化学氟化的概念。2′-氟代和3′-氟代联苯-4-羧酸也能被转化，但速度比未氟化的联苯羧酸衍生物慢。因此，可以通过体外方法确定最容易氧化的位置，然后进行氟化，迭代设计代谢半衰期更长的化合物，无需依赖大量的动物研究。
• Room Temperature Palladium-Catalyzed Cross Coupling of Aryltrimethylammonium Triflates with Aryl Grignard Reagents
  作者：Jonathan T. Reeves、Daniel R. Fandrick、Zhulin Tan、Jinhua J. Song、Heewon Lee、Nathan K. Yee、Chris H. Senanayake

  DOI：10.1021/ol1018739

  日期：2010.10.1

  Aryltrimethylammonium triflates and tetrafluoroborates were found to be highly reactive electrophiles in the Pd-catalyzed cross coupling with aryl Grignard reagents. The coupling reactions proceed at ambient temperature with a nearly stoichiometric quantity of Grignard reagent, and diverse functionality is tolerated. Competition experiments established the reactivity of PhNMe3OTf relative to PhCl,

  在芳基格氏试剂的Pd催化交叉偶联中，发现芳基三甲基铵三氟甲磺酸盐和四氟硼酸盐是高度反应性的亲电子试剂。偶联反应在环境温度下以接近化学计量的格氏试剂进行，并且可以耐受多种功能。竞争实验确定了PhNMe 3 OTf相对于PhCl，PhBr，PhI和PhOTf的反应性。
• Silicon-Based Cross-Coupling Reagent and Production Method of Organic Compound Using the Same
  申请人：Nakao Yoshiaki

  公开号：US20090069577A1

  公开（公告）日：2009-03-12

  In one embodiment of the present invention, a silicon-based cross-coupling reagent is disclosed which is a highly stable tetraorganosilicon compound allowing for a cross-coupling reaction under mild reaction conditions without using fluoride ions, transition metal promoter, or strong bases, and the residue of the silicon reagent can be recovered and reused. The silicon-based cross-coupling reagent is a silicon compound in which an o-hydroxymethylphenyl group is connected to a silicon atom for intramolecular activation.

  在本发明的一个实施例中，揭示了一种基于硅的交叉偶联试剂，它是一种高度稳定的四有机硅化合物，允许在温和的反应条件下进行交叉偶联反应，而无需使用氟离子、过渡金属促进剂或强碱，并且可以回收和重复使用硅试剂的残留物。这种基于硅的交叉偶联试剂是一种硅化合物，其中一个 o-羟甲基苯基基团连接到硅原子以进行分子内活化。
• A general palladium-catalyzed cross-coupling of aryl fluorides and organotitanium (IV) reagents
  作者：Xiao-Yun He

  DOI：10.1007/s00706-021-02796-6

  日期：2021.7

  Pd(OAc)2/1-[2-(di-tert-butylphosphanyl)phenyl]-4-methoxy-piperidine was demonstrated to effectively catalyze cross-coupling of aryl fluoride and aryl(alkyl) titanium reagent. Both electron-deficient and electron-rich aryl fluoride can react effectively with nucleophile and provide extensive functional groups tolerance. 2-Arylated product was realized by selective activation of the C–F bond. Graphic

  Pd(OAc) 2 /1-[2-(二-叔丁基膦酰基)苯基]-4-甲氧基-哌啶被证明可以有效地催化芳基氟和芳基(烷基)钛试剂的交叉偶联。缺电子和富电子芳基氟化物均可与亲核试剂有效反应并提供广泛的官能团耐受性。2-芳基化产物是通过选择性激活 C-F 键实现的。 图形摘要
• Rhodium-Catalyzed Arylation Using Arylboron Compounds:  Efficient Coupling with Aryl Halides and Unexpected Multiple Arylation of Benzonitrile
  作者：Kenji Ueura、Tetsuya Satoh、Masahiro Miura

  DOI：10.1021/ol050590b

  日期：2005.5.1

  [reaction: see text]. The Suzuki-Miyaura-type cross-coupling of arylboron compounds with aryl halides proceeds efficiently in the presence of a rhodium-based catalyst system to produce the corresponding biaryls. Furthermore, it has unexpectedly been observed that the treatment with benzonitrile under similar conditions brings about its multiple arylation, in which nucleophilic arylation on the cyano

  [反应：请参见文字]。在铑基催化剂体系的存在下，芳基硼化合物与芳基卤化物的Suzuki-Miyaura型交叉偶联有效地进行，从而产生相应的联芳基。此外，出乎意料地观察到，在相似条件下用苄腈处理导致其多重芳基化，其中涉及氰基上的亲核芳基化和随后通过CH键裂解的邻位芳基化。