ethyl 2-oxo-3-(2'-propenyl)cyclohexane-1-carboxylate | 99423-49-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: ethyl 2-oxo-3-(2'-propenyl)cyclohexane-1-carboxylate
• 英文别名: Cyclohexanecarboxylic acid, 2-oxo-3-(2-propenyl)-, ethyl ester；ethyl 2-oxo-3-prop-2-enylcyclohexane-1-carboxylate
• CAS: 99423-49-1
• 化学式: C₁₂H₁₈O₃
• 分子量: 210.273
• InChiKey: XIFJYUOBLZQSEV-UHFFFAOYSA-N

物化性质

• 沸点：
  146 °C(Press: 16 Torr)
• 密度：
  1.019±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 2-oxo-3-(2'-propenyl)cyclohexane-1-carboxylate 在 sodium hydroxide 、 三甲基氯硅烷 、 二苯基膦叠氮化物 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 甲苯 为溶剂， 反应 112.0h， 生成
  参考文献：
  名称：

  A Comparison of Cyclohexanone and Tetrahydro-4H-thiopyran-4-one 1,1-Dioxide as Pharmacophores for the Design of Peptide-Based Inhibitors of the Serine Protease Plasmin

  摘要：

  The plasminogen system is important in the proteolytic cascade that facilitates angiogenesis, a process that is essential for tumor growth and metastasis. The serine protease plasmin has a central role in the plasminogen system. This protease acts by degrading several components of the basement membrane and by activating other proteases. Therefore, inhibition of plasmin may be an effective method for blocking angiogenesis and, as a result, inhibiting the growth of primary tumors and secondary metastases. Three pairs of plasmin inhibitors were synthesized to compare the relative potency of inhibitors that are based upon a cyclohexanone or a tetrahydro-4H-thiopyran-4-one 1,1-dioxide nucleus. Compounds 1, 3, and 5 were cyclohexanone-based inhibitors, whereas compounds 2, 4, and 6 were tetrahydro-4H-thiopyran-4-one 1,1-dioxide-based inhibitors. Compounds 5 and 6 are reasonable inhibitors with IC50 values of 25 and 5.5 mu M, respectively. Comparisons of the IC50 values of the three pairs show that the electron-withdrawing sulfone functional group is a beneficial element for the design of plasmin inhibitors. The presence of the sulfone increases inhibitor potency by a factor of 3-5 when compared to inhibitors that are based upon a simple cyclohexanone core.

  DOI：

  10.1021/jo0508954
• 作为产物：
  描述：

  alkaline earth salt of/the/ methylsulfuric acid 在 sodium 、 苯 作用下， 生成 ethyl 2-oxo-3-(2'-propenyl)cyclohexane-1-carboxylate
  参考文献：
  名称：

  Grewe, Chemische Berichte, 1943, vol. 76, p. 1072,1076

  摘要：

  DOI：

文献信息

• Dynamic Kinetic Resolution of γ-Substituted Cyclic β-Ketoesters via Asymmetric Hydrogenation: Constructing Chiral Cyclic β-Hydroxyesters with Three Contiguous Stereocenters
  作者：Dan Yang、Xiong Wu、Xiao-Jie Zheng、Jian-Hua Xie、Qi-Lin Zhou

  DOI：10.1021/acs.orglett.1c01689

  日期：2021.7.2

  An efficient asymmetric hydrogenation of racemic γ-substituted cyclic β-ketoesters via dynamic kinetic resolution to provide chiral cyclic β-hydroxy esters with three contiguous stereocenters is reported. Using a chiral spiro iridium catalyst (R)-5 (Ir-SpiroSAP), a series of racemic γ-aryl/alkyl substituted cyclic β-ketoesters were hydrogenated to the corresponding chiral cyclic β-hydroxy esters in

  据报道，外消旋 γ-取代的环状 β-酮酯通过动态动力学拆分有效不对称氢化，以提供具有三个连续立体中心的手性环状 β-羟基酯。使用手性螺铱催化剂 ( R ) -5 (Ir-SpiroSAP)，一系列外消旋 γ-芳基/烷基取代的环状 β-酮酯以高产率 (84-97%) 氢化成相应的手性环状 β-羟基酯) 具有良好到出色的对映选择性 (69–>99% ee)和顺式、顺式选择性（高达 >99:1）。
• Efficient Synthesis of the Azabicyclo[3.3.1]nonane Ring System in the Alkaloid Methyllycaconitine Using Bis(alkoxymethyl)alkylamines as Aminoalkylating Agents in a Double Mannich Reaction
  作者：Margaret A. Brimble、Constanze Brocke

  DOI：10.1002/ejoc.200500003

  日期：2005.6

  The double Mannich reaction of cyclic β-keto esters with bis(alkoxymethyl)alkylamines provides an efficient and versatile method for the construction of azabicyclo[3.3.1]nonanes and azabicyclo[3.2.1]octanes. The optimum conditions for efficient reaction involve use of the activator trichloromethylsilane in acetonitrile as solvent at ambient temperature. The utility of this synthetic method is further

  环状β-酮酯与双（烷氧基甲基）烷基胺的双曼尼希反应为构建氮杂双环[3.3.1]壬烷和氮杂双环[3.2.1]辛烷提供了一种有效且通用的方法。有效反应的最佳条件包括在环境温度下在乙腈中使用活化剂三氯甲基硅烷作为溶剂。通过将关键的 N-（甲基琥珀酰亚胺）邻氨基苯甲酸药效团附加到 N-（3-苯丙基）-取代的双曼尼希生物碱的几个 AE 环类似物 39、42，该合成方法的实用性得到进一步证明。加合物 18, 27。 (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
• Application of a Double Mannich Reaction Using<i>Bis</i>(aminol) Ethers in the Synthesis of AE Ring Analogues of Methyl Lycaconitine
  作者：Margaret A. Brimble、Constanze Brocke、Diana S.-H. Lin、Malcolm D. McLeod

  DOI：10.1055/s-2004-831340

  日期：——

  An efficient method for the construction of azabicyclo[3.3. 1]nonanes and azabicyclo[3.2. 1]octanes is reported via double Mannich reaction of cyclic ketoesters with bis(aminol) ethers. This method is applied to the synthesis of AE ring analogues of methyl lycaconitine.

  一种构建氮杂双环的有效方法[3.3．1]壬烷和氮杂双环[3.2. 1] 辛烷是通过环状酮酯与双（氨基）醚的双曼尼希反应报道的。该方法用于合成甲基lycaconitine的AE环类似物。
• Use of bis-(aminol) ethers derived from N-(S)-(−)-α-methylbenzylamine in reactions with resorcinarenes and double Mannich reactions
  作者：Benjamin R. Buckley、Philip C. Bulman Page、Harry Heaney、Edward P. Sampler、Sarah Carley、Constanze Brocke、Margaret A. Brimble

  DOI：10.1016/j.tet.2005.03.130

  日期：2005.6

  synthesis of some chiral bis-(aminol)ethers are described. Reaction of a solution of the resorcin[4]arene derived from propanal with N,N-bis(methoxymethyl)-N-(S)-(−)-α-methylbenzylamine in toluene at 85 °C initially afforded a 1:1 mixture of two diastereoisomeric tetrakis(benzoxazines). Further, heating of this mixture under reflux in ethanol for 24 h afforded the crystalline (αS),(S)-diastereoisomer in

  描述了一些手性双（氨基）醚的合成。丙醛衍生的间苯二酚[4]芳烃与N，N-双（甲氧基甲基）-N-（S）-（-）-α-甲基苄基胺的甲苯溶液在85°C下反应，最初得到1：1混合物两个非对映异构体四（苯并恶嗪）。此外，将该混合物在乙醇中回流加热24小时，以77％的产率得到结晶的（αS），（S）-非对映异构体。N，N-双（乙氧基甲基）-N-（S）-（-）-α-甲基苄胺和N，N-双（乙氧基甲基）-N-（使R）-（+）-α-甲基苄基胺与β-酮酯反应，得到非对映异构双曼尼希加合物的1：1混合物。两个双重曼尼希加合物被转化为生物碱甲基lycaconitine 1的三环ABE类似物。
• Synthesis of tricyclic analogues of methyllycaconitine using ring closing metathesis to append a B ring to an AE azabicyclic fragment
  作者：David Barker、Margaret A. Brimble、Malcolm D. McLeod、G. Paul Savage

  DOI：10.1039/b401119h

  日期：——

  pharmacophores: a homocholine motif formed from a tertiary N-ethyl amine in a 3-azabicyclo[3.3.1]nonane ring system and a 2-(3-methyl-2,5-dioxopyrrolidin-1-ly)benzoate ester 4. The synthesis of the ABE tricyclic analogues of MLA 1 began with selective allylation at C-3 of 3 to produce allyl beta-keto ester 4. Double Mannich reaction of 4 with ethylamine and formaldehyde produced bicyclic amine 5 The C-9

  据报道，生物碱甲基lycaconitine 1的几个ABE三环类似物的合成。该类似物包含两个关键药效基团：由3-氮杂双环[3.3.1]壬烷环系统中的叔N-乙基胺形成的高胆碱基序和2-（3-甲基-2,5-二氧杂吡咯烷-1-ly）苯甲酸酯4。合成MLA 1的ABE三环类似物始于在3的C-3上进行烯丙基化，生成烯丙基β-酮酸酯4。4与乙胺和甲醛的双曼尼希反应生成双环胺5 C-9将双环胺5的酮选择性还原以形成双环醇6和7，随后将其二烯丙基化以形成二烯8和9。二烯8和9的闭环易位分别提供三环醚11和12。将其C-8酯还原成羟甲基以形成ABE三环类似物13和14。将烯丙基溴化镁加到20的C-9酮上得到二烯21和22，将其进行闭环复分解以形成三环酯23。和24。将23和24的C-8乙酯还原为羟甲基，分别得到二醇25和26。通过使用N-（三氟乙酰基）将醇13、14、25和26转化为邻氨基苯甲酸酯16、17、27和28，引入2-（3-甲基-2