(1S,5R)-1-苯基-3-氧杂双环[3.1.0]己-2-酮 | 63106-93-4

• 物质功能分类: 有机原料 - 酮类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酯类
• 中文名称: (1S,5R)-1-苯基-3-氧杂双环[3.1.0]己-2-酮
• 中文别名: 盐酸米那普仑中间体3；盐酸米那普仑中间体；盐酸米那普仑中间体2；1-苯基-3-氧杂双环[3.1.0]己-2-酮；2-氧-1-苯基-3-氧双环[3.1.0]己烷；2-氧代-1-苯基-3-氧代双环[3.1.0]-己烷；左旋米娜普伦中间体；左旋米那普仑中间体；(1S,5R)-1-苯基-3-氧杂双环[3.1.]己-2-酮
• 英文名称: 1-phenyl-3-oxa-bicyclo[3.1.0]hexan-2-one
• 英文别名: 1-phenyl-2-oxo-3-oxa-bicyclo(3:1:0)-hexane；1-Phenyl-3-oxabicyclo[3.1.0]hexan-2-one
• CAS: 63106-93-4
• 化学式: C₁₁H₁₀O₂
• mdl: MFCD11046367
• 分子量: 174.199
• InChiKey: WZGFIZUMKYUMRN-UHFFFAOYSA-N

物化性质

• 熔点：
  49-50 °C
• 沸点：
  119 °C(Press: 0.1 Torr)
• 密度：
  1.300±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿、甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.363
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 海关编码：
  2932209090
• 危险性防范说明：
  P261,P280,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H332,H335
• 储存条件：
  2-8℃

反应信息

• 作为反应物：
  描述：

  (1S,5R)-1-苯基-3-氧杂双环[3.1.0]己-2-酮 在 正丁基锂 、 草酰氯 、 二甲基亚砜 、 三乙胺 作用下， 反应 5.0h， 生成 (1S,2R)-2-Formyl-1-phenyl-cyclopropanecarboxylic acid diethylamide
  参考文献：
  名称：

  Conformational Restriction by Repulsion between Adjacent Substituents on a Cyclopropane Ring:  Design and Enantioselective Synthesis of 1-Phenyl-2-(1-aminoalkyl)-N,N-diethylcyclopropanecarboxamides as Potent NMDA Receptor Antagonists

  摘要：

  Adjacent substituents on a cyclopropane ring mutually exert steric repulsion quite significantly, because they are fixed in eclipsed conformation to each other. Based on this structural feature of the cyclopropane ring, conformationally restricted analogs of milnacipran (1), namely 1-phenyl-2-(1-aminoalkyl)-N,N-diethylcyclopropanecarboxamides (2, 3, ent-2, and ent-3) were designed as potent NMDA receptor antagonists and were synthesized highly enantioselectively. Reaction of (R)epichlorohydrin [(R)-5] and phenylacetonitrile (6) in the presence of NaNH2 in benzene gave a chiral cyclopropane derivative that was isolated as lactone 4 with 96% ee in 67% yield, after alkaline hydrolysis of the cyano group. The nucleophilic addition reaction of Grignard reagents to aldehyde 10, which was readily prepared from 4, proceeded highly selectively from the si-face to afford addition products 11 in high yields. Although hydride reduction of the corresponding ketone 15b, prepared from 11b, with L-Selectride also proceeded highly diastereo selectively, the facial selectivity was reversed to give the re-face addition product 11b. On the other hand, reduction of 15 with DIBAL-H afforded the si-face addition product 12 in high yields. These results suggested that these nucleophilic addition reactions proceeded via either the bisected s-trans or s-cis conformation of the cyclopropylcarbonyl derivatives. From 11 and 12, the target conformationally resticted analogs, 2 and 3, were synthesized, respectively. Starting from (S)-epichlorohydrin [(S)-5], their corresponding enantiomers, ent-a and ent-3, were also synthesized. The structures of the conformationally restricted analogs detected by the X-ray crystallographic analysis suggested that their conformations can be restricted as we hypothesized. Thus, a new method for restricting the conformation of cyclopropane derivatives has been developed.

  DOI：

  10.1021/jo9518056
• 作为产物：
  描述：

  allyl 2-diazo-2-phenylacetate 在 dirhodium tetraacetate 、 叠氮基三甲基硅烷 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以78%的产率得到(1S,5R)-1-苯基-3-氧杂双环[3.1.0]己-2-酮
  参考文献：
  名称：

  串联插入/ [3,3]-正向重排涉及通过将卡宾铑插入S-Si键形成甲硅烷基乙缩醛

  摘要：

  已显示2-重氮-2-苯基乙酸烯丙酯在铑（II）催化剂存在下与三甲基甲硅烷基硫醚反应生成α-烯丙基-α-硫代甲硅烷基酯。转变涉及一个串联过程，该过程涉及铑在卡宾基团上正式催化的S-Si键插入，从而生成甲硅烷基烯酮缩醛，然后进行自发的爱尔兰-克莱森重排。在水后处理之后，分离出甲硅烷基酯产物作为相应的羧酸。烯丙基片段的分子内环丙烷化通常与将杂原子添加至卡宾中心竞争。该反应在温和的条件下以高收率进行，从而允许快速进入重排四取代产物。显示炔丙基酯产生相应的α-烯基产物。

  DOI：

  10.1021/acs.orglett.1c00229
• 作为试剂：
  描述：

  (1S,5R)-1-苯基-3-氧杂双环[3.1.0]己-2-酮 在 (1S,5R)-1-苯基-3-氧杂双环[3.1.0]己-2-酮 作用下， 生成 (Z)-1-phenyl-1-(N,N-diethylaminocarbonyl)-2-hydroxymethaneylcyclopropane
  参考文献：
  名称：

  [EN] PROCESS FOR PREPARATION OF MILNACIPRAN INTERMEDIATE AND ITS USE IN PREPARATION OF PURE MILNACIPRAN
  [FR] MÉTHODE DE PRÉPARATION D'UN INTERMÉDIAIRE DE MILNACIPRAN ET SON UTILISATION DANS LA PRÉPARATION DE MILNACIPRAN PUR

  摘要：

  本发明公开了一种制备米纳西普兰中间体的方法，该中间体为公式ΙII的化合物，并且其在制备纯米纳西普兰中的应用。

  公开号：

  WO2011158249A1

文献信息

• 1-Aryl-2-(aminomethyl)cyclopropanecarboxylic acid derivatives. A new series of potential antidepressants
  作者：Bernard Bonnaud、Henri Cousse、Gilbert Mouzin、Mike Briley、Antoine Stenger、Francois Fauran、Jean Pierre Couzinier

  DOI：10.1021/jm00385a013

  日期：1987.2

  A series of 1-aryl-2-(aminomethyl)cyclopropanecarboxylic acid derivatives were synthesized and evaluated as potential antidepressants. Compounds with the Z configuration were synthesized from 1-aryl-2-oxo-3-oxabicyclo[3.1.0]hexane and those with the E configuration from (E)-1-phenyl-2-(hydroxymethyl)cyclopropanecarboxylic acid. The compounds were evaluated in animal tests designed to reveal potential

  合成了一系列的1-芳基-2-（氨基甲基）环丙烷羧酸衍生物，并将其评估为潜在的抗抑郁药。具有Z构型的化合物由1-芳基-2-氧代-3-氧杂双环[3.1.0]己烷合成，具有E构型的化合物由（E）-1-苯基-2-（羟甲基）环丙烷羧酸合成。在动物试验中对化合物进行了评估，旨在揭示其潜在的抗抑郁活性和不良副作用的存在。几种衍生物比丙咪嗪和地昔帕明更具活性。根据其在抗抑郁药理动物实验中的活性及其潜在的无副作用，选择了1-苯基-1-[（（二乙基氨基）羰基] -2-（氨基甲基）环丙烷盐酸盐，中alcipranan（INN）。进一步的发展。
• Dirhodium(II) Tetrakis[methyl 2-oxaazetidine-4-carboxylate]:  A Chiral Dirhodium(II) Carboxamidate of Exceptional Reactivity and Selectivity
  作者：Michael P. Doyle、Simon B. Davies、Wenhao Hu

  DOI：10.1021/ol005730q

  日期：2000.4.1

  [formula: see text] A new chiral azetidinone-carboxylate ligand for dirhodium(II) catalysis enhances reactivity toward diazo decomposition and selectivity toward cyclopropanation enabling diazomalonates, vinyldiazoacetates, and aryldiazoacetates to be effectively used with a dirhodium(II) carboxamidate catalyst.

  [化学式：见正文]一种新的手性氮杂环丁酮-羧酸盐配体，用于二氢吡啶鎓（II）催化，可提高对重氮分解的反应性和对环丙烷化的选择性，从而使重氮丙二酸酯，乙烯基重氮乙酸酯和芳基重氮乙酸酯可有效地与二氨基羧酸铵（II）一起使用。
• Direct Synthesis of Cyclopropanes from <i>gem</i>-Dialkyl Groups through Double C–H Activation
  作者：Antonin Clemenceau、Pierre Thesmar、Maxime Gicquel、Alexandre Le Flohic、Olivier Baudoin

  DOI：10.1021/jacs.0c05887

  日期：2020.9.9

  numerous bioactive molecules, and a number of methods are available for their synthesis. However, one of the simplest cyclopropanation reactions involving the intramolecular coupling of two C-H bonds in a single step has remained an elusive transformation. We demonstrate herein that this reaction is accessible using aryl bromide or triflate precursors and the 1,4-Pd shift mechanism. The use of pivalate

  环丙烷是在许多生物活性分子中发现的重要结构基序，并且有许多方法可用于它们的合成。然而，在一个步骤中涉及两个 CH 键的分子内偶联的最简单的环丙烷化反应之一仍然是一个难以捉摸的转变。我们在此证明该反应可以使用芳基溴或三氟甲磺酸酯前体和 1,4-Pd 转移机制进行。发现使用新戊酸盐作为碱对于将机械途径转向环丙烷而不是先前获得的苯并环丁烯产品至关重要。化学计量机制研究允许鉴定芳基和烷基新戊酸钯，它们通过五元钯环处于平衡状态。与新戊酸盐，导致四元钯环中间体和环丙烷产物的第二次 C(sp3)-H 活化是有利的。开发了一种催化反应，并显示出生成各种芳基环丙烷的广泛范围，包括有价值的双环 [3.1.0] 系统。该方法被应用于最近批准的抗失眠药物 lemborexant 的简洁合成。
• [EN] 1,3-SUBSTITUED PYRAZOLE COMPOUNDS USEFUL FOR REDUCTION OF VERY LONG CHAIN FATTY ACIC LEVELS<br/>[FR] COMPOSÉS PYRAZOLE 1,3-SUBSTITUÉS UTILES POUR LA RÉDUCTION DE NIVEAUX D'ACIDES GRAS À CHAÎNE TRÈS LONGUE
  申请人：VERTEX PHARMA

  公开号：WO2018107056A1

  公开（公告）日：2018-06-14

  Disclosed are chemical entities which are compounds of Formula (I) and pharmaceutically acceptable salts thereof, wherein Formula (I) has the structure: R1a, R1b, R2, R3, R4a, R4b and Y are as defined herein. These chemical entities are useful for reduction of very long chain fatty acid levels. These chemical entities and pharmaceutically acceptable compositions comprising such chemical entities can be useful for treating various diseases, disorders and conditions, such as adrenoleukodystrophy (ALD).

  揭示了化学实体，它们是具有式（I）的化合物及其药学上可接受的盐，其中式（I）具有结构：R1a，R1b，R2，R3，R4a，R4b和Y如本文所定义。这些化学实体对于降低非常长链脂肪酸水平是有用的。这些化学实体和包括这些化学实体的药学上可接受的组合物可用于治疗各种疾病、疾病和症状，如肾上腺白质脑白质营养不良（ALD）。
• PROCESS FOR PREPARING OPTICALLY PURE MILNACIPRAN AND ITS PHARMACEUTICALLY ACCEPTABLE SALTS
  申请人：Pai Ganesh Gurpur

  公开号：US20120289744A1

  公开（公告）日：2012-11-15

  The present invention relates to an improved and commercially, viable process for the resolution of racemic cis milnacipran of formula I and its pharmaceutically acceptable salts of formula II. The present invention comprises using racemic cis milnacipran or its pharmaceutically acceptable salts as starting material, a low cost and commercially available resolving agent of formula III and industrially safe and economically low cost material such as water as a solvent. The said process results into optical isomers of racemic cis milnacipran having excellent optical purity without involving multiple crystallization steps. The present invention also comprises the concept of green chemistry as the invention works well with water as a solvent thereby minimizing the use of any other solvent. (Formular I and II should be inserted here) Wherein X is anion selected from Cl, Br, I, HSO 4 , Phosphate or organic acid (Formular III should be inserted here) *represent asymmetric centre Compound of formula III represent mandelic acid and its derivatives.

  本发明涉及一种改进的商业化可行的过程，用于分离式解决式I的顺式米纳西普兰的外消旋体和其药用可接受盐II。本发明包括使用外消旋式顺式米纳西普兰或其药用可接受盐作为起始物质，采用具有低成本和商业化可用性的分离剂III的工业安全和经济低成本材料，例如水作为溶剂。所述过程导致具有优异光学纯度的外消旋式顺式米纳西普兰的光学异构体，而无需进行多次结晶步骤。本发明还包括绿色化学的概念，因为该发明在水作为溶剂的情况下运作良好，从而最大限度地减少了对任何其他溶剂的使用。其中X是从Cl、Br、I、HSO4、磷酸盐或有机酸中选择的阴离子。III的化学式应插入此处，*代表不对称中心，化合物III的化学式代表苹果酸及其衍生物。