2-(4-氯苯氧基)-3-氧代-4-苯基丙酸乙酯 | 823214-64-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 2-(4-氯苯氧基)-3-氧代-4-苯基丙酸乙酯
• 英文名称: ethyl 2-(4-chlorophenoxy)-3-oxo-4-phenylpropanoate
• 英文别名: Ethyl 2-(4-chlorophenoxy)-3-oxo-3-phenylpropanoate
• CAS: 823214-64-8
• 化学式: C₁₇H₁₅ClO₄
• 分子量: 318.757
• InChiKey: OXRCXQZBRFAZKM-UHFFFAOYSA-N

物化性质

• 熔点：
  60.2-61.3 °C(Solv: hexane (110-54-3))
• 沸点：
  445.6±35.0 °C(Predicted)
• 密度：
  1.251±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(4-氯苯氧基)-3-氧代-4-苯基丙酸乙酯 在 baker's yeast 作用下， 以 乙醇 、 水 为溶剂， 反应 48.0h， 以33%的产率得到ethyl (2R,3S)-2-(4-chlorophenoxy)-3-hydroxy-3-phenylpropanoate
  参考文献：
  名称：

  Baker’s yeast-mediated reduction of ethyl 2-(4-chlorophenoxy)-3-oxoalkanoates intermediates for potential PPARα ligands

  摘要：

  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.

  DOI：

  10.1016/j.tetasy.2004.08.027
• 作为产物：
  描述：

  ethyl 2-chloro-3-oxo-3-phenylpropionate 、 sodium 4-chlorophenolate 以 甲苯 为溶剂， 反应 24.0h， 以78%的产率得到2-(4-氯苯氧基)-3-氧代-4-苯基丙酸乙酯
  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

• A novel route to 4-oxy/thio substituted-1H-pyrazol-5(4H)-ones via efficient cross-Claisen condensation
  作者：R. Venkat Ragavan、V. Vijayakumar

  DOI：10.1002/jhet.558

  日期：2011.3

  α‐Oxy/thio substituted β‐keto esters were synthesized through an efficient cross‐Claisen condensation of oxy/thio substituted acetic acid ethyl esters with acid chlorides, which in turn converted in situ into 4‐oxy/thio substituted‐1H‐pyrazol‐5(4H)‐ones by the addition of hydrazine and its derivatives. This method has been found to be extremely fast, general, and useful toward the synthesis of inaccessible

  通过氧/硫代取代的乙酸乙酯与酰基氯的有效交叉克莱森缩合反应合成α-氧/硫代取代的β-酮酯，然后原位转化为4-氧/硫代取代的1 H-吡唑‐5（4 H）‐加肼及其衍生物。已发现该方法非常快速，通用，可用于合成难以接近的吡唑啉酮和合成需要4-氧/硫取代的吡唑啉酮。J.杂环化​​学。（2011）。
• Screening yeasts for the stereoselective reduction of oxoester clofibrate analogues
  作者：Maria Grazia Perrone、Ernesto Santandrea、Antonio Scilimati、Christoph Syldatk、Vincenzo Tortorella

  DOI：10.1016/j.tetasy.2005.02.010

  日期：2005.4

  Reduction of oxoesters 1b-d and 1fg in the presence of different yeast strains (Saccharomyces cerevisiae DSM 11285, S. cerevisiae CBS 7336, Cryptococcus curvatus ATCC 20509, Candida hombicola ATCC 22214, Trigonopsis variabilis DSM 70714, Kluyveromyces marxianus CBS 6556) affords hydroxy esters 2b-d and 2fg with diastereoisomeric excesses (de) up to > 99%. Hydrolytic enzyme(s) contained in the yeasts catalyzed to some extent the hydrolysis of the oxoesters to the corresponding acids, which undergo decarboxylation followed by reduction of the carbonyl moiety. (c) 2005 Elsevier Ltd. All rights reserved.
• 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.
• Synthesis and biological evaluation of new clofibrate analogues as potential PPARα agonists
  作者：Maria Grazia Perrone、Ernesto Santandrea、Natalina Dell’Uomo、Fabio Giannessi、Ferdinando Maria Milazzo、Anna Floriana Sciarroni、Antonio Scilimati、Vincenzo Tortorella

  DOI：10.1016/j.ejmech.2004.09.018

  日期：2005.2

  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.