methyl 4-tert-butylcyclohexane-1-carboxylate | 17177-75-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: methyl 4-tert-butylcyclohexane-1-carboxylate
• 英文别名: methyl trans-4-tert-butylcyclohexanecarboxylate；trans-4-tert-Butyl-cyclohexancarbonsaeure-methylester；trans-4-tert-Butyl-cyclohexan-carbonsaeure-(1)-methylester
• CAS: 17177-75-2
• 化学式: C₁₂H₂₂O₂
• 分子量: 198.305
• InChiKey: BWJSSYBIZVGKBG-MGCOHNPYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.01
• 重原子数：
  14.0
• 可旋转键数：
  1.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  26.3
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  methyl 4-tert-butylcyclohexane-1-carboxylate 在 lithium aluminium tetrahydride 、 sodium azide 、 三乙胺 、 sodium iodide 作用下， 以 乙醚 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 trans-4-tert.-Butylcyclohexylmethyl-azid
  参考文献：
  名称：

  tert‐Butyl as a Functional Group: Non‐Directed Catalytic Hydroxylation of Sterically Congested Primary C−H Bonds

  摘要：

  The tert‐butyl group is a common aliphatic motif extensively employed to implement steric congestion and conformational rigidity in organic and organometallic molecules. Because of the combination of a high bond dissociation energy (~100 kcal mol−1) and limited accessibility, in the absence of directing groups, neither radical nor organometallic approaches are effective for the chemical modification of tert‐butyl C−H bonds. Herein we overcome these limits by employing a highly electrophilic manganese catalyst, [Mn(CF3bpeb)(OTf)2], that operates in the strong hydrogen bond donor solvent nonafluoro‐tert‐butyl alcohol (NFTBA) and catalytically activates hydrogen peroxide to generate a powerful manganese‐oxo species that effectively oxidizes tert‐butyl C−H bonds. Leveraging on the interplay of steric, electronic, medium and torsional effects, site‐selective and product chemoselective hydroxylation of the tert‐butyl group is accomplished with broad reaction scope, delivering primary alcohols as largely dominant products in preparative yields. Late‐stage hydroxylation at tert‐butyl sites is demonstrated on 6 densely functionalized molecules of pharmaceutical interest. This work uncovers a novel disconnection approach, harnessing tert‐butyl as a potential functional group in strategic synthetic planning for complex molecular architectures.

  DOI：

  10.1002/anie.202402858
• 作为产物：
  描述：

  cis-4-tert-butyl-2-hydroxycyclohexanal 在 lead(II) oxide 作用下， 以 乙醚 、 水 为溶剂， 反应 6.0h， 生成 methyl 4-tert-butylcyclohexane-1-carboxylate
  参考文献：
  名称：

  Gakhokidze, R. A., Doklady Chemistry, 1982, vol. 265, p. 233 - 236

  摘要：

  DOI：

文献信息

• Selenoesters in organic synthesis. 1. A novel synthesis of ketones.
  作者：A.F. Sviridov、M.S. Ermolenko、D.V. Yashunsky、N.K. Kochetkov

  DOI：10.1016/s0040-4039(00)88340-9

  日期：1983.1

  A mild and efficient esters into ketones transformation via selenoesters have been described.

  已经描述了一种温和有效的酯，其通过硒酸酯转化成酮。
• Etude du caractere nucleophile des radicaux lors de la reaction de transfert sur la liaison O-O des peracides
  作者：Jacques Fossey、Daniel Lefort

  DOI：10.1016/0040-4020(80)80056-1

  日期：1980.1

  Peracids RC03H yield free radicals R' which react either with the peracid or with solvent giving the alcohol ROH and the hydrocarbon RH. The nucleophilic character of the free radicals was modified either by substitution of the carbon bearing the odd electron by inductive groups or by changing the free radical hybridation by the means of blocked structures such as cyclic or bicyclic free radicals.

  过酸RC0 3H产生自由基R'，其与过酸或与溶剂反应，得到醇ROH和烃RH。自由基的亲核特性可以通过用感应基团取代带有奇数电子的碳或通过使用环状或双环自由基等封闭结构来改变自由基杂化来进行修饰。对于每个R，比率ROH / RH的测量建立了具有过酸OO键的R的反应性规模。这种反应性不依赖于自由基的稳定性，而是强烈依赖于亲核特性。一级自由基的反应性比二级自由基的要低，并且与叔级自由基的反应性要低得多。作为双环[2.2.1]庚基-1的桥头自由基不与过酸反应。这些结果被解释为表明带有电荷转移的过渡态（极性效应），过酸是亲电子的，自由基是亲核的。讨论了PMO理论。
• Oxidation of primary alcohols to methyl esters using tert-butyl hypochlorite, pyridine and methyl alcohol
  作者：Jovan N. Milovanovi?、Miorad Vasojevi?、Svetislav Gojkovi?

  DOI：10.1039/p29910001231

  日期：——

  When treated with tert-butyl hypochlorite, in the presence of pyridine and methyl alcohol, saturated aliphatic primary alcohols are oxidized to methyl esters in very high yields. Oxidation of benzylic alcohols, under the same conditions, yields a mixture of aldehydes and methyl esters. It appears that this reaction is a three-step process with an aldehyde and acyl chloride as the intermediates. Investigation

  当在吡啶和甲醇的存在下用次氯酸叔丁酯处理时，饱和的脂肪族伯醇以很高的收率被氧化成甲酯。在相同条件下氧化苄醇会生成醛和甲酯的混合物。看来该反应是用醛和酰氯为中间体的三步法。对相对反应速率的研究表明，与预期的相比，苯甲醇的氧化速度快于脂族醇，而相应的醛在反应性方面却显示出相反的趋势。提出了反应机理，并且脂族和苄基醛的反应性差异归因于立体电子因素。
• 17O NMR spectra of tertiary alcohols, ethers, sulfoxides and sulfones in the cyclohexyl and 5-substituted 1,3-dioxanyl series and related compounds
  作者：Muthiah Manoharan、Ernest L. Eliel

  DOI：10.1002/mrc.1260230403

  日期：1985.4

  17O NMR spectra of fifteen cyclohexane‐derived tertiary alcohols and related ethers and acetals, six 1,3‐dioxane‐derived orthoesters, four cyclohexane‐ and 1,3‐dioxane‐derived sulfones and the four corresponding sulfoxides, three acyclic sulfones, six alcohols derived from norbornane and 1,3‐dithiane and two esters have been recorded. Attention is drawn to δ‐compression effects and saturation effects

  十五种环己烷衍生的叔醇和相关醚和缩醛、六种 1,3-二恶烷衍生的原酸酯、四种环己烷和 1,3-二恶烷衍生的砜以及四种相应的亚砜、三种无环砜、六种醇的 17O NMR 光谱已经记录了衍生自降冰片烷和 1,3-二噻烷和两种酯的物质。需要注意其中几种化合物的 δ 压缩效应和饱和效应。
• FIVE-MEMBERED HETEROCYCLES USEFUL AS SERINE PROTEASE INHIBITORS
  申请人：Hangeland Jon J.

  公开号：US20090036438A1

  公开（公告）日：2009-02-05

  The present invention provides a method for treating a thrombotic or an inflammatory disorder administering to a patient in need thereof a therapeutically effective amount of at least one compound of Formula (I) or Formula (V): or a stereoisomer or pharmaceutically acceptable salt or solvate form thereof, wherein the variables A, L, Z, R 3 , R 4 , R 6 , R 11 , X 1 , X 2 , and X 3 are as defined herein. The compounds of Formula (I) are useful as selective inhibitors of serine protease enzymes of the coagulation cascade and/or contact activation system; for example thrombin, factor Xa, factor XIa, factor IXa, factor VIIa and/or plasma kallikrein. In particular, it relates to compounds that are selective factor XIa inhibitors. This invention also provides compounds within the scope of Formula I and relates to pharmaceutical compositions comprising these compounds.

  本发明提供了一种治疗血栓性或炎症性疾病的方法，该方法向需要治疗的患者施用至少一种公式（I）或公式（V）中的化合物的治疗有效量：或其立体异构体或药学上可接受的盐或溶剂形式，其中变量A、L、Z、R3、R4、R6、R11、X1、X2和X3如本文所定义。公式（I）的化合物可用作凝血级联和/或接触激活系统的丝氨酸蛋白酶酶的选择性抑制剂；例如凝血酶、因子Xa、因子XIa、因子IXa、因子VIIa和/或血浆激肽。特别是，涉及到选择性因子XIa抑制剂的化合物。本发明还提供了公式I范围内的化合物，并涉及包含这些化合物的制药组合物。