2-(4-氯苯氧基)-3-氧代丁酸乙酯 | 119138-47-5

• 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: 2-(4-氯苯氧基)-3-氧代丁酸乙酯
• 英文名称: ethyl 2-(4-chlorophenoxy)-3-oxobutanoate
• 英文别名: Ethyl 2-(4-chlorophenoxy)acetoacetate
• CAS: 119138-47-5
• 化学式: C₁₂H₁₃ClO₄
• 分子量: 256.686
• InChiKey: BYSZRJCFCVJFOC-UHFFFAOYSA-N

物化性质

• 沸点：
  150-155 °C(Press: 5 Torr)
• 密度：
  1.228±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2918990090

反应信息

• 作为反应物：
  描述：

  2-(4-氯苯氧基)-3-氧代丁酸乙酯 在 氢氧化钾 、 sodium tetrahydroborate 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 1.5h， 生成 2-(4-Chlorophenoxy)-3-hydroxybutanoic acid
  参考文献：
  名称：

  Synthesis and biological evaluation of new clofibrate analogues as potential PPARα agonists

  摘要：

  Clofibrate is a lipid-profile modifying agent belonging to the fibrate class of drugs. Fibrates are known to exhibit their beneficial effects by activating peroxisome proliferator-activated receptor-alpha (PPARalpha) and used in the treatment of dyslipidemia and atherosclerosis and for the prevention of heart failure. Hereby, the preparation of two new sets of clofibrate analogues, ethyl 2-(4-chlorophenoxy)-3-oxoalkanoates and ethyl 2-(4-chlorophenoxy)-3-hydroxyalkanoates is described starting from commercially available 3-oxoalkanoates in fair to good yields. Treatment of 3-oxoalkanoates with SO2Cl2 yielded the corresponding 2-chloro-3-oxoalkanoates, that were then converted into 2-(4-chlorophenoxy)-3-oxoalkanoates by reacting with sodium or caesium 4-chlorophenate. Reduction of the keto group with NaBH4 afforded the corresponding 2-(4-chlorophenoxy)-3-hydroxyalkanoates in very high yields and with variable diastereoselectivity. Biological evaluation of the compounds was performed by a transactivation assay in a transiently transfected monkey kidney fibroblast cell line. The newly synthesised clofibrate analogues failed to show noticeable levels of PPAR activation at concentrations where clofibrate showed an evident activity, suggesting that the structural modifications caused the loss of PPAR activity. (C) 2004 Elsevier SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2004.09.018
• 作为产物：
  描述：

  sodium 4-chlorophenolate 、 2-氯乙酰乙酸乙酯 反应 5.0h， 以69%的产率得到2-(4-氯苯氧基)-3-氧代丁酸乙酯
  参考文献：
  名称：

  Synthesis and biological evaluation of new clofibrate analogues as potential PPARα agonists

  摘要：

  Clofibrate is a lipid-profile modifying agent belonging to the fibrate class of drugs. Fibrates are known to exhibit their beneficial effects by activating peroxisome proliferator-activated receptor-alpha (PPARalpha) and used in the treatment of dyslipidemia and atherosclerosis and for the prevention of heart failure. Hereby, the preparation of two new sets of clofibrate analogues, ethyl 2-(4-chlorophenoxy)-3-oxoalkanoates and ethyl 2-(4-chlorophenoxy)-3-hydroxyalkanoates is described starting from commercially available 3-oxoalkanoates in fair to good yields. Treatment of 3-oxoalkanoates with SO2Cl2 yielded the corresponding 2-chloro-3-oxoalkanoates, that were then converted into 2-(4-chlorophenoxy)-3-oxoalkanoates by reacting with sodium or caesium 4-chlorophenate. Reduction of the keto group with NaBH4 afforded the corresponding 2-(4-chlorophenoxy)-3-hydroxyalkanoates in very high yields and with variable diastereoselectivity. Biological evaluation of the compounds was performed by a transactivation assay in a transiently transfected monkey kidney fibroblast cell line. The newly synthesised clofibrate analogues failed to show noticeable levels of PPAR activation at concentrations where clofibrate showed an evident activity, suggesting that the structural modifications caused the loss of PPAR activity. (C) 2004 Elsevier SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2004.09.018

文献信息

• Selective heteronuclear NOE enhancements in benzoheterocycles. Effect of ring size on indirect three-spin effects
  作者：Jordi Redondo、Francisco Sánchez-Ferrando、Montserrat Valls、Albert Virgili

  DOI：10.1002/mrc.1260260615

  日期：1988.6

  The 80 MHz 1H NMR and 20 MHz 13C NMR spectra of five 4-methylcoumarins, six 4-methyl-2(1H)-quinolones and nine 3-methylbenzo[b]furans, including six new compounds, were fully assigned. Homonuclear 1H1H} NOEs and selective heteronuclear 13C1H} NOEs were measured after low-power pre-saturation of the methyl protons. Indirect, negative heteronuclear NOE enhancements were found in suitable three-spin systems of the 13C1H1H} type, and their magnitude was found to be dependent on ring size. The first examples of indirect, heteronuclear NOE enhancements on non-protonated carbons are described.

  对五种4-甲基香豆素、六种4-甲基-2(1H)-喹诺酮以及九种3-甲基苯并[b]呋喃（其中包括六种新化合物）的80 MHz 1H NMR和20 MHz 13C NMR谱进行了全面归属。在低功率预饱和甲基质子后，测量了同核1H1H} NOE和选择性异核13C1H} NOE。在适当的13C-1H-1H}三自旋体系中发现了间接的负异核NOE增强，并且发现其幅度依赖于环的大小。首次描述了非质子化碳上的间接异核NOE增强的实例。
• .alpha.-adrenergic receptor antagonists
  申请人：SmithKline Beecham Corporation

  公开号：US04978660A1

  公开（公告）日：1990-12-18

  .alpha.-adrenoceptor antagonists having the formula: ##STR1## which are useful to produce .alpha.-adrenoceptor antagonism, pharmaceutical compositions including these antagonists, and methods of using these antagonists to produce .alpha.-adrenoceptor antagonism in mannals.

  具有以下结构式的α-肾上腺素受体拮抗剂：##STR1##，用于产生α-肾上腺素受体拮抗作用，包括这些拮抗剂的药物组合物，以及使用这些拮抗剂在哺乳动物中产生α-肾上腺素受体拮抗作用的方法。
• Alpha-adrenergic receptor antagonists
  申请人：SmithKline Beecham Corporation

  公开号：US04981849A1

  公开（公告）日：1991-01-01

  Alpha-adrenoceptor antagonists having the formula: ##STR1## which are useful to produce .alpha.-adrenoceptor antagonism, pharmaceutical compositions including these antagonists, and methods of using these antagonists to produce .alpha.-adrenoceptor antagonism in mammals.

  具有以下结构的α-肾上腺素受体拮抗剂：##STR1##，这些拮抗剂可用于产生α-肾上腺素受体拮抗作用，包括这些拮抗剂的药物组合物，以及使用这些拮抗剂在哺乳动物中产生α-肾上腺素受体拮抗作用的方法。
• Stereoselective Prostereogenic 3-Oxo Ester Reduction Mediated by a Novel Yeast Alcohol Dehydrogenase Derived fromKluyveromyces marxianus CBS 6556
  作者：Maria Grazia Perrone、Ernesto Santandrea、Antonio Scilimati、Christoph Syldatk

  DOI：10.1002/adsc.200600379

  日期：2007.5.7

  (DEAE-anion exchange and affinity chromatography). The optimal pH was 7, its optimal temperature was 40 °C and its co-factor was NADPH. This novel ADH efficiently mediated the reduction of 3-oxo esters with a high degree of stereoselectivity, providing chiral alcohols having the (S) absolute configuration at the newly formed stereogenic centre by delivering the hydride from the re-face of the prochiral carbonyl

  酵母醇脱氢酶（ADH）已从马克斯克鲁维酵母CBS 6556中纯化到21,731倍的纯化因子值。纯化程序包括两个色谱步骤（DEAE-阴离子交换和亲和色谱）。最佳pH为7，最佳温度为40°C，辅助因子为NADPH。这种新颖的ADH有效地介导的3-氧代酯具有高度的立体选择性的还原，提供具有（手性醇小号通过从输送氢化物）的绝对构型在新形成的手性中心重的前手性羰基化合物-面。
• Baker’s yeast-mediated reduction of ethyl 2-(4-chlorophenoxy)-3-oxoalkanoates intermediates for potential PPARα ligands
  作者：Maria Grazia Perrone、Ernesto Santandrea、Antonio Scilimati、Vincenzo Tortorella、Francesco Capitelli、Valerio Bertolasi

  DOI：10.1016/j.tetasy.2004.08.027

  日期：2004.11

  Several 2-(4-chlorophenoxy)-3-oxoesters were prepared in fair to good yields and then reduced in the presence of baker's yeast to the corresponding alcohols having de's up to 92% and ee's > 99%. The absolute configuration of nearly enantiomerically pure ethyl 2-(4-chlorophenoxy)-3-hydroxybutanoate was assigned by both comparison of the sign of the specific rotation and HPLC retention times of authentic samples prepared from threonines. Reduction of ethyl 2-(4-chlorophenoxy)-3-oxo-4-phenylbutanoate afforded only enantiomerically pure ethyl (2R,3S)-2-(4-chlorophenoxy)-3-hydroxy-4-phenylbutanoate (out of the four possible stereoisomers), whose absolute configuration was established by single crystal X-ray analysis. Furthermore, reduction of ethyl 2-methyl-2-(4-chlorophenoxy)-3-hydroxybutanoate with a quaternary stereogenic carbon (C-2) gave both of the two expected diastereoisomers with ee = 95% and 96%. Insight into the mechanism of baker's yeast-mediated reduction of prochiral ketoesters is also reported. (C) 2004 Elsevier Ltd. All rights reserved.