(E)-(5-chloro-pent-3-en-1-ynyl)benzene | 40316-56-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (E)-(5-chloro-pent-3-en-1-ynyl)benzene
• 英文别名: Benzene, (5-chloro-3-penten-1-ynyl)-, (E)-；[(E)-5-chloropent-3-en-1-ynyl]benzene
• CAS: 40316-56-1
• 化学式: C₁₁H₉Cl
• 分子量: 176.645
• InChiKey: BBGIOOYFTFYQIR-QHHAFSJGSA-N

物化性质

• 沸点：
  271.0±32.0 °C(Predicted)
• 密度：
  1.10±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  0
• 氢给体数：
  0
• 氢受体数：
  0

反应信息

• 作为反应物：
  描述：

  (E)-(5-chloro-pent-3-en-1-ynyl)benzene 以 Petroleum ether 为溶剂， 生成 ((1S,2S)-2-Chloro-cyclopropylethynyl)-benzene
  参考文献：
  名称：

  Bohlmann,F. et al., Justus Liebigs Annalen der Chemie, 1971, vol. 745, p. 176 - 192

  摘要：

  DOI：
• 作为产物：
  描述：

  苯丙炔醛缩二乙醛 在 硫酸 、 sodium ethanolate 、 二异丁基氢化铝 、 甲基磺酰氯 、 N,N-二甲基甲酰胺 作用下， 以 甲苯 为溶剂， 反应 11.5h， 生成 (E)-(5-chloro-pent-3-en-1-ynyl)benzene
  参考文献：
  名称：

  Process Development and Scale-Up of the PPAR Agonist NNC 61-4655

  摘要：

  A scalable synthetic route of the nonselective but PPARalpha-preferring potent PPAR agonist NNC 61-4655 aimed for treatment of type 2 diabetes was developed. The synthetic pathway comprises the convergent synthesis and coupling of the two key intermediates E-5-(chloropent-3-en-1-ynyl)benzene 8 (prepared in a five-step synthesis in 18% overall yield) and (S)-2-ethoxy-3-(4-hydroxyphenyl)propanoic acid isopropyl ester 9. The 2-aminoethanol salt of NNC 61-4655 was selected in a preclinical salt selection program as the appropriate salt form for further development. More than 900 g of NNC 61-4655, 2-aminoethanol was finally synthesized under GMP in 98.7% purity. In comparison to the original medicinal chemistry route, starting from phenylpropargyl aldehyde 1, the overall yield towards NNC 61-4655 could be enhanced from 24 to 37%. An improved scalable two-step synthesis for 8 was developed on a laboratory scale ( greater than or equal to 33-35% overall yield) shortly after the GMP batch.

  DOI：

  10.1021/op034048j

文献信息

• Gold-Catalyzed Asymmetric Thioallylation of Propiolates via Charge-Induced Thio-Claisen Rearrangement
  作者：Hanbyul Kim、Jiwon Jang、Seunghoon Shin

  DOI：10.1021/jacs.0c09783

  日期：2020.12.9

  A gold(I)-catalyzed enantioselective thioallylation of propiolates with allyl sulfides is described. The key mechanistic element is a sulfonium-induced Claisen rearrangement which helps minimize the allyl dissociation and render higher enantioselectivity. This protocol features remarkable scope of the allyl moiety, allowing enantiocontrolled synthesis of all-carbon quaternary centers, and exhibits

  描述了金 (I) 催化的丙炔酸酯与烯丙基硫化物的对映选择性硫代烯丙基化。关键的机制元素是锍诱导的克莱森重排，这有助于最大限度地减少烯丙基离解并提供更高的对映选择性。该协议具有显着的烯丙基部分范围，允许全碳四元中心的对映控制合成，并与许多路易斯碱和 π 键表现出卓越的官能团兼容性。Claisen 重排的这种分子间变体同时形成 CS 和 CC 键，为获得有趣的光学活性有机硫化合物提供了有效的途径，这些化合物可以通过乙烯基硫化物作为功能手柄进一步转化。对于烯丙基硫化物，反应速率为零级，这表明可逆抑制，为催化剂提供静止状态。哈米特图显示了与 σp 值的相关性，表明限制周转的 σ 重排，其中硫上电子密度的降低加速了重排。
• New compounds, their preparation and use
  申请人：——

  公开号：US20010041709A1

  公开（公告）日：2001-11-15

  The present invention relates to compounds of formula (I) 1 The compounds are useful in the treatment and/or prevention of conditions mediated by nuclear receptors, in particular the Peroxisome Proliferator-Activated Receptors (PPAR).

  本发明涉及式(I)的化合物。 这些化合物在治疗和/或预防由核受体介导的疾病中具有用途，特别是过氧化物酶体增殖激活受体（PPAR）。
• A stereoselective synthesis of (E)-1-halo-6,6-dimethyl-2-hepten-4-yne: a key intermediate for terbinafine
  作者：Shan-Yen Chou、Chin-Lu Tseng、Shyh-Fong Chen

  DOI：10.1016/s0040-4039(00)00511-6

  日期：2000.5

  A study of the stereoselective halogenation of 6,6-dimethyl-1-hepten-4-yn-3-ol (1) using a series of halogenating agents is described. Of the many agents investigated, boron trichloride is the most successful reagent for stereoselective halogenation (E:Z=9:1max). The resulting (E)-1-halo-6,6-dimethyl-2-hepten-4-yne (2), a key intermediate for terbinafine, an antifungal agent, is obtained in good yield

  描述了使用一系列卤化剂对6,6-二甲基-1-庚烯-4-yn-3-ol（1）进行立体选择性卤化的研究。在研究的许多试剂中，三氯化硼是最成功的立体选择性卤化试剂（E：Z = 9：1 max）。以良好的收率和立体选择性获得了所得的（E）-1-卤代-6,6-二甲基-2-庚基-4-炔（2），这是特比萘芬（一种抗真菌剂）的关键中间体。同样研究了两种结构相关的炔烃，并显示了相似的通用性。
• Enyne Chlorides: Substrates for Copper-Catalyzed Asymmetric Allylic Alkylation
  作者：Hailing Li、Alexandre Alexakis

  DOI：10.1002/anie.201107129

  日期：2012.1.23

  A select few: Several prochiral enyne chlorides were employed as substrates in the title reaction using Grignard reagents as the alkylation reagents (see scheme; CuTC=copper(I) thiophenecarboxylate). Excellent 1,3 substitution regioselectivities and good to excellent enantioselectivities were obtained. The substrate scope is additionally extended to diene chlorides.

  少量选择：在标题反应中，使用格氏试剂作为烷基化试剂，使用了几种前手性烯属氯化物作为底物（参见方案； CuTC =噻吩铜（I）铜）。获得了极好的1，3取代区域选择性和良好至极好的对映选择性。底物的范围还扩展到二烯氯化物。
• Synthesis of tritium and carbon-14 labelled NNC 61-4655: a potent dual-acting PPAR? and PPAR? agonist
  作者：Steen K. Johansen、Lars Martiny

  DOI：10.1002/jlcr.725

  日期：2003.8

  The synthesis of the potent dual-acting PPARα and PPARγ agonist NNC 61-4655 labelled with tritium and carbon-14 is reported. Tritium labelled NNC 61-4655 was obtained in three steps with introduction of tritium through catalytic tritium-halogen exchange of an aryl bromide precursor. This provided [3H]NNC 61-4655 in 39% overall radiochemical yield with a specific activity of 49 Ci/mmol. Carbon-14 labelled NNC 61-4655 was obtained in five steps starting from bromo[1-14C]acetic acid. The synthetic sequence, which included a Horner–Wadsworth–Emmons olefination and a Mitsunobu alkylation, provided [14C]NNC 61-4655 in 33% overall radiochemical yield with a specific activity of 57.4 mCi/mmol. Copyright © 2003 John Wiley & Sons, Ltd.

  报道了用氚和碳 14 标记的有效双作用 PPARα 和 PPARγ 激动剂 NNC 61-4655 的合成。通过芳基溴前体的催化氚-卤素交换引入氚，分三步获得了氚标记的 NNC 61-4655。这提供了 [3H]NNC 61-4655，总放射化学产率为 39%，比活性为 49 Ci/mmol。以溴[1-14C]乙酸为起始原料，分五步获得碳 14 标记的 NNC 61-4655。合成序列包括 Horner-Wadsworth-Emmons 烯化和 Mitsunobu 烷基化，以 33% 的总放射化学产率提供 [14C]NNC 61-4655，比活性为 57.4 mCi/mmol。版权所有 © 2003 约翰·威利父子有限公司