(4-oxo-4,5,6,7-tetrahydro-1-benzofuran-5-yl)acetic acid | 145295-99-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 英文名称: (4-oxo-4,5,6,7-tetrahydro-1-benzofuran-5-yl)acetic acid
• 英文别名: 4-oxo-4,5,6,7-tetrahydrobenzo[b]furan-5-yl acetic acid；2-(4-Oxo-4,5,6,7-tetrahydrobenzofuran-5-yl)acetic acid；2-(4-oxo-6,7-dihydro-5H-1-benzofuran-5-yl)acetic acid
• CAS: 145295-99-4
• 化学式: C₁₀H₁₀O₄
• 分子量: 194.187
• InChiKey: PLMBFVOFAXJSSW-UHFFFAOYSA-N

物化性质

• 熔点：
  120-125°C

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  67.5
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• WGK Germany：
  3

反应信息

• 作为反应物：
  描述：

  (4-oxo-4,5,6,7-tetrahydro-1-benzofuran-5-yl)acetic acid 在 lithium aluminium tetrahydride 、 1-羟基苯并三唑 、 对甲苯磺酸 、 N,N'-二环己基碳二亚胺 作用下， 以 乙醚 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 104.0h， 生成
  参考文献：
  名称：

  New Serotonin 5-HT_2A, 5-HT_2B, and 5-HT_2C Receptor Antagonists:  Synthesis, Pharmacology, 3D-QSAR, and Molecular Modeling of (Aminoalkyl)benzo and Heterocycloalkanones

  摘要：

  A series of 52 conformationally constrained butyrophenones have been synthesized and pharmacologically tested as antagonists at 5-HT2A, 5-HT2B, and 5-HT2C serotonin receptors, useful for dissecting the role of each 5-HT2 subtype in pathophysiology. These compounds were also a consistent set for the identification of structural features relevant to receptor recognition and subtype discrimination. Six compounds were found highly active (pK(1) > 8.76) and selective at the 5-HT2A receptor vs 5-HT2B and/or 5-HT2C receptors. Piperidine fragments confer high affinity at the 5-HT2A receptor subtype, with benzofuranone- and thiotetralonepiperidine as the most selective derivatives over 5-HT2C and 5-HT2B receptors, respectively; K-1 2A/2C and/or K-B 2A/2B ratios greater than 100 were obtained. Compounds showing a more pronounced selectivity at 5-HT2A/5-HT2C than at 5-HT2A/5-HT2B bear 6-fluorobenzisoxazolyl- and p-fluorobenzoylpiperidine moieties containing one methylene bridging the basic piperidine, to the alkanone moiety. An ethylene bridge between the alkanone and the amino moieties led to ligands with higher affinities for the 5-HT2B receptor. Significant selectivity at the 5-HT2B receptor vs 5-HT2C was observed with 1-1[(1-oxo-1,2,3,4-tetrahydro-3-naphthyl)methyl-4-[3-(p-fluorobenzoyl)propyl]piperazine (more than 100-fold higher). Although piperidine fragments also confer higher affinity at 5-HT2C receptors, only piperazine-containing ligands were selective over 5-HT2A. Moderate selectivity was observed at 5-HT2C vs 5-HT2B (10-fold) with some compounds bearing a 4-[3-(6-fluorobenzisoxazolyl)]piperidine moiety in its structure. Molecular determinants for antagonists acting at 5-HT2A receptors were identified by 3D-QSAR (GRID-GOLPE) studies. Docking simulations at 5-HT2A and 5-HT2C receptors suggest a binding site for the studied type of antagonists (between transmembrane helices 2, 3, and 7) different to that of the natural agonist serotonin (between 3, 5, and 6).

  DOI：

  10.1021/jm011014y
• 作为产物：
  描述：

  6,7-二氢-4(5H)-苯并呋喃酮 在 sodium hydroxide 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 21.5h， 生成 (4-oxo-4,5,6,7-tetrahydro-1-benzofuran-5-yl)acetic acid
  参考文献：
  名称：

  呋喃 [2,3-h]- 和哒嗪并 [3,4-f]cinnolin-3-ol 支架作为开发新型 HIV-1 整合酶抑制剂的底物的研究

  摘要：

  为了开发新型 HIV-1 整合酶抑制剂，我们获得了一组基于呋喃 [2,3-h]cinnolin-3(2H)-one 和哒嗪基 [3,4-f]cinnolin-的稠环系统。带有潜在螯合药效团的 3-ol 支架，可参与酶的抑制机制。在此，我们报告了这些杂芳族系统的设计、合成、结构研究和初步生物学结果。

  DOI：

  10.3998/ark.5550190.0012.901

文献信息

• Direct Use of Carboxylic Acids in the Photocatalytic Hydroacylation of Styrenes To Generate Dialkyl Ketones
  作者：Jesus I. Martinez Alvarado、Alyssa B. Ertel、Andrea Stegner、Erin E. Stache、Abigail G. Doyle

  DOI：10.1021/acs.orglett.9b03871

  日期：2019.12.20

  A general protocol for the hydroacylation of styrenes from aliphatic carboxylic acids is reported. These reactions proceed via β-scission of a phosphoranyl radical that is accessed by photoredox catalysis, followed by addition of the resulting acyl radical to the styrenyl olefin. We show that phosphine tunability is critical for efficient intermolecular coupling due to competitive quenching of the

  报道了脂肪族羧酸对苯乙烯进行加氢酰化的通用方案。这些反应通过光氧化还原催化作用下的正膦基自由基的β-断裂进行，然后将所得酰基自由基加成到苯乙烯基烯烃上。我们表明，由于烯烃对光催化剂的竞争性猝灭，膦的可调性对于有效的分子间偶联至关重要。伯、仲和结构刚性的叔羧酸均产生有价值的不对称二烷基酮。
• Direct Conversion of Carboxylic Acids to Alkyl Ketones
  作者：Javad Amani、Gary A. Molander

  DOI：10.1021/acs.orglett.7b01588

  日期：2017.7.7

  efficient and mild method for acyl–Csp3 bond formation based on the direct conversion of carboxylic acids has been established. This protocol is enabled by the synergistic, Ir-photoredox/nickel catalytic cross-coupling of in situ activated carboxylic acids and alkyltrifluoroborates. This versatile method is amenable to the cross-coupling of structurally diverse carboxylic acids with various potassium

  建立了基于羧酸直接转化的有效且温和的酰基-C sp3键形成方法。通过原位活化的羧酸和三氟硼酸烷基酯的Ir-光氧化还原/镍催化交叉偶联，可以实现该方案。这种通用的方法适合于结构多样的羧酸与各种烷基三氟硼酸钾的交叉偶联，从而以高收率提供相应的酮。在这种操作简单的交叉偶联方案中，一步法从稳定，易于获得的羧酸中获得脂肪族酮。