1alpha-Phenyl-2beta-(hydroxymethyl)cyclopropanecarbonitrile | 910028-42-1

• 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: 1alpha-Phenyl-2beta-(hydroxymethyl)cyclopropanecarbonitrile
• 英文别名: (1R,2S)-2-(hydroxymethyl)-1-phenylcyclopropane-1-carbonitrile
• CAS: 910028-42-1
• 化学式: C₁₁H₁₁NO
• 分子量: 173.214
• InChiKey: YDIYUDSRGPPHKA-MNOVXSKESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  44
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1alpha-Phenyl-2beta-(hydroxymethyl)cyclopropanecarbonitrile 在 盐酸 、 氢氧化钾 、 sodium azide 、 lithium amide 、 四溴化碳 、 三苯基膦 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 (1R,2S)-1-phenyl-2-(azidomethyl)-N,N-diethylcyclopropanecarboxamide
  参考文献：
  名称：

  （+）-和（-）-米那普仑及其构象受限的类似物的合成

  摘要：

  （R）-表氯醇[（R）-5 ]与苯乙腈（6）在NaNH 2的存在下在苯中的反应生成环丙烷衍生物，其被分离为内酯4 [（1 S，2 R）-2-氧-在氰基进行碱性水解后，96％ee的1-苯基-3-氧杂双环[3,1,0]己烷]的收率为67％。化合物4容易地转化为（+）-米那普仑[（+）- 1 ]，由此证实了（+）- 1的绝对立体化学。（1 S，2 R）-1-苯基-2-[（（S）-1-氨乙基]-环丙烷-N，N-diethylcarboxamindes（2），构象受限的1的类似物，还从4合成高对映体纯度。从（S）-表氯醇[（S）-5 ]开始，还合成了它们相应的对映异构体，即（-）-米那普仑[（-）- 1 ]和ent-2 。

  DOI：

  10.1016/0040-4039(95)02221-x
• 作为产物：
  描述：

  (1S)-1-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-cyano-2-phenylethyl 4-methylbenzenesulfonate 在 四丁基氟化铵 、 双(三甲基硅烷基)氨基钾 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 1.0h， 生成 1alpha-Phenyl-2beta-(hydroxymethyl)cyclopropanecarbonitrile
  参考文献：
  名称：

  Stereocontrolled Synthesis of Trisubstituted Cyclopropanes:  Expedient, Atom-Economical, Asymmetric Syntheses of (+)-Bicifadine and DOV21947

  摘要：

  An expedient, atom-economical, asymmetric synthesis of 1-aryl-3-azabicyclo[3.1.0]hexanes, including (+)-Bicifadine and DOV21947, in a single-stage through process without isolation of any intermediates has been developed. The key of this synthesis is the in-depth mechanistic understanding of the complicated epoxy nitrile coupling at each reaction stage. Therefore, the desired trisubstituted cyclopropane can be prepared in high ee and yield by controlling the reaction pathway through manipulating the nitrile anion aggregation state.

  DOI：

  10.1021/ol061650w

文献信息

• [EN] A NEW PROCESS FOR PREPARING OPTICALLY PURE MILNACIPRAN AND ITS PHARMACEUTICALLY ACCEPTABLE SALTS.<br/>[FR] NOUVEAU PROCÉDÉ DE PRÉPARATION DE MILNACIPRAN OPTIQUEMENT PUR ET DE SES SELS DE QUALITÉ PHARMACEUTIQUE
  申请人：ARCH PHARMALABS LTD

  公开号：WO2012059933A1

  公开（公告）日：2012-05-10

  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, HSO4, 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可行的过程，用于分离式异构体顺式米纳西普兰（化学式I）及其药用可接受盐（化学式II）。本发明包括使用顺式米纳西普兰的异构体或其药用可接受盐作为起始物质，以及具有低成本且商业上可获得的分离剂（化学式III）和工业安全以及经济低成本材料（如水）作为溶剂。该过程导致顺式米纳西普兰的光学异构体具有优异的光学纯度，而无需进行多次结晶步骤。本发明还包括绿色化学概念，因为该发明与水作为溶剂良好配合，从而最小化了对任何其他溶剂的使用。 （化学式I和II应在此处插入） 其中X是从Cl、Br、I、HSO4、磷酸盐或有机酸中选择的阴离子 （化学式III应在此处插入） *代表不对称中心，化合物的化学式III代表苯乙酸及其衍生物。
• 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。
• Synthesis and Characterization of Process Related Impurities of (±)-Milnacipran
  作者：P. Raja Gopal、A. Christy Prabakar、ERR Chandrashekar、B. Vijaya bhaskar、P. Veera Somaiah

  DOI：10.1002/jccs.201200484

  日期：2013.6

  Milnacipran is a cyclopropane derivative, used as an anti depressant drug. During the process development of milnacipran, four process related potential impurities were detected in high performance liquid chromatography. All these impurities were identified, synthesized and subsequently characterized by their respective spectral data (IR, LC‐MS, 1H NMR, and 13C NMR) as described in this article.

  米那普仑是一种环丙烷衍生物，用作抗抑郁药。在米那普仑的工艺开发过程中，高效液相色谱法检测到四种与工艺相关的潜在杂质。如本文所述，所有这些杂质均经过鉴定，合成并随后通过其各自的光谱数据（IR，LC-MS，1 H NMR和13 C NMR）进行了表征。
• One-pot cyclization of dilithiated nitriles with isothiocyanates and epibromohydrin. Synthesis of 2-cyano-1-(hydroxymethyl)cyclopropanes and 2-cyanomethylidene-4-(hydroxymethyl)thiazolidines
  作者：Uwe Albrecht、Ilia Freifeld、Helmut Reinke、Peter Langer

  DOI：10.1016/j.tet.2006.03.072

  日期：2006.6

  The cyclization of dilithiated nitriles with epibromohydrin afforded 2-cyano-1-(hydroxymethyl)cyclopropanes. 2-Cyanomethylidene-(4-hydroxymethyl)thiazolidines were prepared by one-pot cyclization of dilithiated nitriles with isothiocyanates and epibromohydrin. (c) 2006 Elsevier Ltd. All rights reserved.
• WO2007/127421
  申请人：——

  公开号：——

  公开（公告）日：——