diethyl α-bromodifluoromethyl-α-ethylmalonate | 82477-47-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: diethyl α-bromodifluoromethyl-α-ethylmalonate
• 英文别名: diethyl 2-[bromo(difluoro)methyl]-2-ethylpropanedioate
• CAS: 82477-47-2
• 化学式: C₁₀H₁₅BrF₂O₄
• 分子量: 317.128
• InChiKey: DGEJAJTWFOTHOT-UHFFFAOYSA-N

物化性质

• 沸点：
  104 °C(Press: 15 Torr)
• 密度：
  1.411±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  17.0
• 可旋转键数：
  6.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  52.6
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  diethyl α-bromodifluoromethyl-α-ethylmalonate 在 potassium fluoride 作用下， 以 二甲基亚砜 为溶剂， 反应 2.0h， 以44%的产率得到2-(三氟甲基)丁酸乙酯
  参考文献：
  名称：

  含β-CF3基团的酯的制备

  摘要：

  丙二酸酯可以在两步法中转化为含有δ-CF3基团的酯，该过程涉及丙二酸酯的溴二氟甲基化，然后在DMSO中用氟离子进行脱羧烷基化-氟化。

  DOI：

  10.1016/s0040-4039(01)80149-0
• 作为产物：
  描述：

  二氟一氯溴甲烷 、 乙基丙二酸二乙酯 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 以35%的产率得到diethyl α-bromodifluoromethyl-α-ethylmalonate
  参考文献：
  名称：

  Rico, Isabelle; Cantacuzene, Danielle; Wakselman, Claude, Journal of the Chemical Society. Perkin transactions I, 1982, p. 1063 - 1066

  摘要：

  DOI：

文献信息

• Preparation of .alpha.-trifluoromethyl esters from malonic esters
  作者：T. Stephen Everett、Suzanne T. Purrington、Carl L. Bumgardner

  DOI：10.1021/jo00194a006

  日期：1984.10
• Synthesis, Structure-Activity Relationships, and Pharmacological Evaluation of a Series of Fluorinated 3-Benzyl-5-Indolecarboxamides: Identification of 4-[[5-[((2R)-2-Methyl-4,4,4-trifluorobutyl)carbamoyl]-1-methylindol-3-yl]methyl]-3methoxy-N-[(2-methylphenyl)sulfonyl]benzamide, a Potent, Orally Active Antagonist of Leukotrienes D4 and E4
  作者：Robert T. Jacobs、Peter R. Bernstein、Laura A. Cronk、Edward P. Vacek、Lisa F. Newcomb、David Aharony、Carl K. Buckner、Edward J. Kusner

  DOI：10.1021/jm00035a008

  日期：1994.4

  The continued exploration of a series of 3-(arylmethyl)-1H-indole-5-carboxamides by the introduction of fluorinated amide substituents has resulted in the discovery of 4-[[5-[((2R)-2-methyl-4,4,4-trifluorobutyl)carbamoyl]-1-methylindol-3-yl]methyl]-3-methoxy-N-[(2-methylphenyl)sulfonyl]benzamide (38p, ZENECA ZD 3523),which has been chosen for clinical evaluation. This compound exhibited a K-i of 0.42 nM for displacement of [H-3]LTD(4) on guinea pig lung membranes, a pK(B) Of 10.13 +/- 0.14 versus LTE(4) on guinea pig trachea, and an oral ED(50) Of 1.14 mu mol/kg opposite LTD(4)-induced bronchoconstriction in guinea pigs. The R enantiomer was found to be modestly more potent than the S enantiomer 38o. Modification of the amide substituent to afford achiral compounds was unsuccessful in achieving comparable levels of activity. Profiling of 38p opposite a variety of functional assays has demonstrated the selectivity of this compound as a leukotriene receptor antagonist. The enantioselective synthesis of 38p, which employed a diastereoselective alkylation of (4R,5S)-3-(1-oxo-4,4,4-trifluorobutyl)-4-methyl-5-phenyl-2-oxazolidinone (27) as the key step to establish the chirality of the amide substituent, provided an efficient route for generating 38p in >99% enantiomeric purity.
• RICO, I.;CANTACUZENE, D.;WAKSELMAN, C., J. CHEM. SOC. PERKIN TRANS., 1982, N 4, 1063-1065
  作者：RICO, I.、CANTACUZENE, D.、WAKSELMAN, C.

  DOI：——

  日期：——
• PURRINGTON, S. T.;EVERETT, T. S.;BUMGARDNER, C. L., TETRAHEDRON LETT., 1984, 25, N 13, 1329-1332
  作者：PURRINGTON, S. T.、EVERETT, T. S.、BUMGARDNER, C. L.

  DOI：——

  日期：——
• EVERETT, T. S.;PURRINGTON, S. T.;BUMGARDNER, C. L., J. ORG. CHEM., 1984, 49, N 20, 3702-3706
  作者：EVERETT, T. S.、PURRINGTON, S. T.、BUMGARDNER, C. L.

  DOI：——

  日期：——