α-(hexafluoroisopropoxy)ethanoic acid | 41246-93-9

• 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: α-(hexafluoroisopropoxy)ethanoic acid
• 英文别名: (hexafluoroisopropyloxy)acetic acid；hexafluoroisopropoxyethanoic acid；alpha-(Hexafluoroisopropoxy)acetic acid；2-(1,1,1,3,3,3-hexafluoropropan-2-yloxy)acetic acid
• CAS: 41246-93-9
• 化学式: C₅H₄F₆O₃
• 分子量: 226.075
• InChiKey: YRNYDOLJFCUCNM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  α-(hexafluoroisopropoxy)ethanoic acid 在 草酰氯 、 氯化锑(V) 、 三氟化锑 、 氯 、 二异丁基氢化铝 、 N,N-二甲基甲酰胺 作用下， 生成
  参考文献：
  名称：

  Photoaffinity Ligand for the Inhalational Anesthetic Sevoflurane Allows Mechanistic Insight into Potassium Channel Modulation

  摘要：

  Sevoflurane is a commonly used inhaled general anesthetic. Despite this, its mechanism of action remains largely elusive. Compared to other anesthetics, sevoflurane exhibits distinct functional activity. In particular, sevoflurane is a positive modulator of voltage-gated Shaker-related potassium channels (K(v)1.x), which are key regulators of action potentials. Here, we report the synthesis and validation of azisevoflurane, a photoaffinity ligand for the direct identification of sevoflurane binding sites in the K(v)1.2 channel. Azisevoflurane retains major sevoflurane protein binding interactions and pharmacological properties within in vivo models. Photoactivation of azisevoflurane induces adduction to amino acid residues that accurately reported sevoflurane protein binding sites in model proteins. Pharmacologically relevant concentrations of azisevoflurane analogously potentiated wild-type K(v)1.2 and the established mutant K(v)1.2 G329T. In wild-type K(v)1.2 channels, azisevoflurane photolabeled Leu317 within the internal S4-S5 linker, a vital helix that couples the voltage sensor to the pore region. A residue lining the same binding cavity was photolabeled by azisevoflurane and protected by sevoflurane in the K(v)1.2 G329T. Mutagenesis of Leu317 in WT K(v)1.2 abolished sevoflurane voltage-dependent positive modulation. Azisevoflurane additionally photolabeled a second distinct site at Thr384 near the external selectivity filter in the K(v)1.2 G329T mutant. The identified sevoflurane binding sites are located in critical regions involved in gating of K-v channels and related ion channels. Azisevoflurane has thus emerged as a new tool to discover inhaled anesthetic targets and binding sites and investigate contributions of these targets to general anesthesia.

  DOI：

  10.1021/acschembio.7b00222
• 作为产物：
  描述：

  Ethyl 2-(1,1,1,3,3,3-hexafluoropropan-2-yloxy)acetate 在 sodium hydroxide 作用下， 生成 α-(hexafluoroisopropoxy)ethanoic acid
  参考文献：
  名称：

  Photoaffinity Ligand for the Inhalational Anesthetic Sevoflurane Allows Mechanistic Insight into Potassium Channel Modulation

  摘要：

  Sevoflurane is a commonly used inhaled general anesthetic. Despite this, its mechanism of action remains largely elusive. Compared to other anesthetics, sevoflurane exhibits distinct functional activity. In particular, sevoflurane is a positive modulator of voltage-gated Shaker-related potassium channels (K(v)1.x), which are key regulators of action potentials. Here, we report the synthesis and validation of azisevoflurane, a photoaffinity ligand for the direct identification of sevoflurane binding sites in the K(v)1.2 channel. Azisevoflurane retains major sevoflurane protein binding interactions and pharmacological properties within in vivo models. Photoactivation of azisevoflurane induces adduction to amino acid residues that accurately reported sevoflurane protein binding sites in model proteins. Pharmacologically relevant concentrations of azisevoflurane analogously potentiated wild-type K(v)1.2 and the established mutant K(v)1.2 G329T. In wild-type K(v)1.2 channels, azisevoflurane photolabeled Leu317 within the internal S4-S5 linker, a vital helix that couples the voltage sensor to the pore region. A residue lining the same binding cavity was photolabeled by azisevoflurane and protected by sevoflurane in the K(v)1.2 G329T. Mutagenesis of Leu317 in WT K(v)1.2 abolished sevoflurane voltage-dependent positive modulation. Azisevoflurane additionally photolabeled a second distinct site at Thr384 near the external selectivity filter in the K(v)1.2 G329T mutant. The identified sevoflurane binding sites are located in critical regions involved in gating of K-v channels and related ion channels. Azisevoflurane has thus emerged as a new tool to discover inhaled anesthetic targets and binding sites and investigate contributions of these targets to general anesthesia.

  DOI：

  10.1021/acschembio.7b00222

文献信息

• PROCESS FOR THE PREPARATION OF FLUOROMETHYL 2,2,2-TRIFLUORO-1-(TRIFLUOROMETHYL) ETHYL ETHER
  申请人：Pacheco Ogari

  公开号：US20090247791A1

  公开（公告）日：2009-10-01

  The present invention refers to a process for the preparation of fluoromethyl 2,2,2-trifluoro-1-(trifluoromethyl)ethyl ether (sevoflurane) which includes a step that consists of reacting hexafluoroisopropanol with a formaldehyde equivalent selected among paraformaldehyde or 1,3,5-trioxane, a chlorinating agent selected from the group consisting of oxalyl chloride, phosphorus trichloride, phosphorus pentachloride, phosphorus oxychloride, sulfuryl chloride and thionyl chloride, and a strong acid selected from the group consisting of concentrated or fuming sulfuric acid resulting in the formation of the intermediate sevochlorane which is converted to sevoflurane in a second step which consists of reacting sevochlorane with an alkali metal fluoride, or a linear or branched chain tetra-alkyl quarternary ammonium fluoride in the presence of a sub-stoichiometric quantity of an alkali metal iodide, or a linear or branched alkyl chain tetra-alkyl quarternary ammonium iodide, preferably in a solvent.

  本发明涉及一种制备氟甲基2,2,2-三氟-1-（三氟甲基）乙基醚（七氟醚）的方法，其中包括以下步骤：将六氟异丙醇与选择自聚甲醛或1,3,5-三噁烷的甲醛等效物、从草酰氯、三氯化磷、五氯化磷、氧化亚磷、氯化亚磷酰和亚磺酰氯的组中选择的氯化剂和从浓硫酸或烟雾硫酸中选择的强酸反应，形成中间体七氟氯烷，然后在第二步中将七氟氯烷与碱金属氟或线性或支链四烷基季铵氟在亚化学计量量的碘化金属或线性或支链烷基四烷基季铵碘的存在下反应，优选在溶剂中进行，从而转化为七氟醚。
• PROCESS FOR THE PREPARATION OF CHLOROMETHYL 2,2,2-TRIFLUORO-1-(TRIFLUOROMETHYL) ETHYL ETHER
  申请人：Pacheco Ogari

  公开号：US20100004490A1

  公开（公告）日：2010-01-07

  The present invention refers to a process for the preparation of chloromethyl 2,2,2-trifluoro-1-(trifluoromethyl) ethyl ether (sevochlorane), which consists of reacting hexafluoroisopropanol with: a formaldehyde equivalent selected between paraformaldehyde or 1,3,5-trioxane, a chlorinating agent selected from the group consisting of oxalyl chloride, phosphorus trichloride, phosphorus pentachloride, phosphorus oxychloride, sulfuryl chloride and thionyl chloride, and a strong acid selected from the group consisting of concentrated or fuming sulfuric acid. Said process provides sevochlorane in high purity and yield, which can be converted to sevoflurane by known means.

  本发明涉及一种制备氯甲基2,2,2-三氟-1-(三氟甲基)乙醚（七氟醚）的方法，其包括将六氟异丙醇与以下物质反应：从间甲醛或1,3,5-三噁烷中选择的一种甲醛等效物、从草酰氯、三氯化磷、五氯化磷、氧氯化磷、氯磺酰氯和硫酰氯组成的氯化试剂，以及从浓硫酸或烟酸组成的强酸。该方法提供了高纯度和高产率的七氟醚，可以通过已知的方法转化为七氟醚。
• Process for the preparation of fluoromethyl 2,2,2-trifluoro-1-(trifluoromethyl) ethyl ether
  申请人：Cristália Produtos Químicos Farmacêuticos Ltda.

  公开号：US08044247B2

  公开（公告）日：2011-10-25

  The present invention refers to a process for the preparation of fluoromethyl 2,2,2-trifluoro-1-(trifluoromethyl)ethyl ether (sevoflurane) which includes a step that consists of reacting hexafluoroisopropanol with a formaldehyde equivalent selected among paraformaldehyde or 1,3,5-trioxane, a chlorinating agent selected from the group consisting of oxalyl chloride, phosphorus trichloride, phosphorus pentachloride, phosphorus oxychloride, sulfuryl chloride and thionyl chloride, and a strong acid selected from the group consisting of concentrated or fuming sulfuric acid resulting in the formation of the intermediate sevochlorane which is converted to sevoflurane in a second step which consists of reacting sevochlorane with an alkali metal fluoride, or a linear or branched chain tetra-alkyl quarternary ammonium fluoride in the presence of a sub-stoichiometric quantity of an alkali metal iodide, or a linear or branched alkyl chain tetra-alkyl quarternary ammonium iodide, preferably in a solvent.

  本发明涉及一种制备氟甲基2,2,2-三氟-1-(三氟甲基)乙基醚（七氟醚）的过程，其中包括以下步骤：将六氟异丙醇与在对甲醛或1,3,5-三噁烷中选择的一种甲醛当量、在草酸酰氯、三氯化磷、五氯化磷、氧化磷酰、氯化亚砜和氯化硫酰中选择的一种氯化剂，以及在浓硫酸或烟酸中选择的一种强酸反应，形成中间体七氟氯烷，然后在第二步中，将七氟氯烷与碱金属氟或线性或支链四烷基季铵氟在次计量量的碘化金属或线性或支链烷基四烷基季铵碘的存在下反应，优选在溶剂中，从而转化为七氟醚。
• Process for the preparation of chloromethyl 2,2,2-trifluoro-1-(trifluoromethyl) ethyl ether
  申请人：Cristalia Produtos Quimicos Farmaceuticos Ltda.

  公开号：US08039678B2

  公开（公告）日：2011-10-18

  The present invention refers to a process for the preparation of chloromethyl 2,2,2-trifluoro-1-(trifluoromethyl) ethyl ether (sevochlorane), which consists of reacting hexafluoroisopropanol with: a formaldehyde equivalent selected between paraformaldehyde or 1,3,5-trioxane, a chlorinating agent selected from the group consisting of oxalyl chloride, phosphorus trichloride, phosphorus pentachloride, phosphorus oxychloride, sulfuryl chloride and thionyl chloride, and a strong acid selected from the group consisting of concentrated or fuming sulfuric acid. Said process provides sevochlorane in high purity and yield, which can be converted to sevoflurane by known means.

  本发明涉及一种制备氯甲基2,2,2-三氟-1-（三氟甲基）乙基醚（sevochlorane）的过程，其包括将六氟异丙醇与以下物质反应：从聚甲醛或1,3,5-三噁烷中选择的甲醛等效物，从草酸氯、三氯化磷、五氯化磷、氧化亚磷酰、氯磺酰氯和硫酰氯组成的氯化试剂，以及从浓硫酸或烟雾状硫酸组成的强酸。该过程提供高纯度和高产率的sevochlorane，可通过已知的方法转化为sevoflurane。
• 2-Arylbenzoxazoles as CETP inhibitors: Substitution and modification of the α-alkoxyamide moiety
  作者：Julianne A. Hunt、Silvia Gonzalez、Florida Kallashi、Milton L. Hammond、James V. Pivnichny、Xinchun Tong、Suoyu S. Xu、Matt S. Anderson、Ying Chen、Suzanne S. Eveland、Qiu Guo、Sheryl A. Hyland、Denise P. Milot、Carl P. Sparrow、Samuel D. Wright、Peter J. Sinclair

  DOI：10.1016/j.bmcl.2009.12.046

  日期：2010.2

  The development of a series of 2-arylbenzoxazole alpha-alkoxyamide and beta-alkoxyamine inhibitors of cholesteryl ester transfer protein (CETP) is described. Highly fluorinated alpha-alkoxyamides proved to be potent inhibitors of CETP in vitro, and the highly fluorinated 2-arylbenzoxazole beta-alkoxyamine 4 showed a desirable combination of in vitro potency (IC(50) = 151 nM) and oral bioavailability in the mouse. (c) 2009 Elsevier Ltd. All rights reserved.