2-cyclohexyl-2-hydroxyethanoic acid N-t-butylamide | 4957-67-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-cyclohexyl-2-hydroxyethanoic acid N-t-butylamide
• 英文别名: N-tert-butyl-2-hydroxy-2-cyclohexylacetamide；Cyclohexyl-glykolsaeure-tert.-butylamid；N-tert-butyl-2-cyclohexyl-2-hydroxyacetamide
• CAS: 4957-67-9
• 化学式: C₁₂H₂₃NO₂
• 分子量: 213.32
• InChiKey: FBKIGMDJQCSGFH-UHFFFAOYSA-N

物化性质

• 熔点：
  121-122 °C
• 沸点：
  373.2±25.0 °C(Predicted)
• 密度：
  1.008±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-cyclohexyl-2-hydroxyethanoic acid N-t-butylamide 在 chromium(VI) oxide 、 盐酸 、 tin(ll) chloride 作用下， 以 乙醚 、 溶剂黄146 为溶剂， 反应 27.5h， 生成 alpha-环己基噻吩-3-乙酸
  参考文献：
  名称：

  Roxburgh, Craig J.; Ganellin, C. Robin; Shiner, Mark A. R., Journal of Pharmacy and Pharmacology, 1996, vol. 48, # 8, p. 851 - 857

  摘要：

  DOI：
• 作为产物：
  描述：

  异氰酸叔丁酯 在 吡啶-N-氧化物 、 四氯化硅 、 碳酸氢钠 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 14.0h， 生成 2-cyclohexyl-2-hydroxyethanoic acid N-t-butylamide
  参考文献：
  名称：

  异氰酸酯的催化，对映选择性α-加成：路易斯碱催化的Passerini型反应

  摘要：

  已经证明了异氰酸酯催化醛的对映选择性α-加成反应的普遍性（Passerini型反应）。四氯化硅和手性双磷酰胺（R，R）-1b的催化体系为叔丁基异氰酸酯加成多种醛（芳族，杂芳族，烯属，炔属，脂族）提供了高收率和良好至优异的对映选择性。水处理得到α-羟基叔胺-丁基酰胺，而低温甲醇淬灭，然后进行碱性后处理，得到α-羟基甲基酯。该反应对于其他异氰酸酯也成功，尽管对映选择性降低。发现反应条件，特别是异氰酸酯的添加速率对于良好的产率和高的选择性至关重要。

  DOI：

  10.1021/jo050549m

文献信息

• A One-Pot<i>O</i>-Phosphinative Passerini/Pudovik Reaction: Efficient Synthesis of Highly Functionalized α-(Phosphinyloxy)amide Derivatives
  作者：Takahiro Soeta、Syunsuke Matsuzaki、Yutaka Ukaji

  DOI：10.1002/chem.201304618

  日期：2014.4.22

  A one‐pot O‐phosphinative Passerini/Pudovik reaction has been developed, based on reacting aldehydes, isocyanides, and phosphinic acids followed by the addition of second aldehydes to form the corresponding α‐(phosphinyloxy)amide derivatives. This is the first reported instance of a Passerini‐type, isocyanide‐based multicomponent reaction using a phosphinic acid instead of a carboxylic acid. The nucleophilicity

  基于醛，异氰酸酯和次膦酸的反应，然后添加第二个醛以形成相应的α-（次膦酰氧基）酰胺衍生物，已经开发了一种单锅O-磷化的Passerini / Pudovik反应。这是首次报道使用次膦酸代替羧酸的基于Passerini型，基于异氰化物的多组分反应。次膦酸酯基团的亲核性允许随后的催化Pudovik型反应，以高收率提供高度官能化的α-（次膦酰氧基）酰胺衍生物。各种各样的醛和异氰酸酯适用于该反应。
• The First Catalytic, Asymmetric α-Additions of Isocyanides. Lewis-Base-Catalyzed, Enantioselective Passerini-Type Reactions
  作者：Scott E. Denmark、Yu Fan

  DOI：10.1021/ja035410c

  日期：2003.7.1

  The first, catalytic, enantioselective alpha-additions of isocyanides to aldehydes have been demonstrated (Passerini-type reactions). The catalytic system of silicon tetrachloride and a chiral bisphosphoramide 5a provided high yields and good to excellent enantioselectivities for the addition of tert-butyl isocyanide to a wide range of aldehydes (aromatic, olefinic, acetylenic, aliphatic). Aqueous

  第一个，异氰化物与醛的催化、对映选择性 α 加成反应已经被证明（Passerini 型反应）。四氯化硅和手性双磷酰胺 5a 的催化体系提供了高产率和良好的对映选择性，用于将叔丁基异氰化物加成到多种醛（芳香族、烯烃、炔属、脂肪族）。水性后处理提供α-羟基叔丁基酰胺，而甲醇淬灭随后进行碱性后处理提供α-羟基甲基酯。
• Direct Alkylative Passerini Reaction of Aldehydes, Isocyanides, and Free Aliphatic Alcohols Catalyzed by Indium(III) Triflate
  作者：Hikaru Yanai、Tomoko Oguchi、Takeo Taguchi

  DOI：10.1021/jo900354e

  日期：2009.5.15

  In(OTf)3 was found to be a useful Lewis acid catalyst for direct alkylative Passerini reaction of aldehydes, isocyanides, and free aliphatic alcohols. In the present reaction, aromatic and α,β-unsaturated aldehydes performed as nice substrates to give the corresponding α-alkoxy amide products in good yield.

  发现In（OTf）3是用于醛，异氰酸酯和游离脂族醇的直接烷基化Passerini反应的有用的路易斯酸催化剂。在本反应中，芳族和α，β-不饱和醛作为良好的底物，以良好的收率得到相应的α-烷氧基酰胺产物。
• Passerini Reaction to Access α‐Hydroxy Amides by Facile Decarbonylation/Decarboxylation of Oxalic Acid
  作者：Luan A. Martinho、Thaissa Pasquali F. Rosalba、Carlos Kleber Z. Andrade

  DOI：10.1002/ejoc.202201199

  日期：2022.12.27

  α-Hydroxy amides were easily obtained through a novel and direct approach through decarbonylation/decarboxylation of α-acyloxy amide adducts (originated from Passerini reactions with oxalic acid) under solvent-free conditions with microwave heating.

  α-羟基酰胺很容易通过一种新颖而直接的方法获得，即在无溶剂条件下用微波加热对 α-酰氧基酰胺加合物（源自 Passerini 与草酸的反应）进行脱羰/脱羧。
• Synthesis and biological evaluation of α-ketoamides as inhibitors of the Dengue virus protease with antiviral activity in cell-culture
  作者：Christian Steuer、Christian Gege、Wolfgang Fischl、Karl H. Heinonen、Ralf Bartenschlager、Christian D. Klein

  DOI：10.1016/j.bmc.2011.05.015

  日期：2011.7

  The development of small molecule inhibitors of the viral protease is of considerable interest for the treatment of emergent flaviviral diseases such as Dengue or West Nile fever. Until today little progress has been made in finding drug-like compounds that inhibit the protease and provide a starting point for lead optimization. We describe here the initial steps of a drug discovery effort that focused on the styryl pharmacophore, combined with a ketoamide function to serve as electrophilic trap for the catalytic serine. This resulted in a fragment-like lead compound with reasonable target affinity and good ligand efficiency, which was extensively modified to explore structure-activity relationships. Selected compounds were cross-tested against the West Nile virus protease and thrombin, indicating that selectivity for one or more flaviviral proteases can be achieved. Finally, the antiviral activity of several protease inhibitors was confirmed in a cell-culture model of Dengue virus replication. The SAR presented here may serve as starting point for further drug discovery efforts with the aim of targeting flaviviral proteases. (C) 2011 Elsevier Ltd. All rights reserved.