3-[(4-hydroxymethylphenyl)-(tetrahydropyran-2-yloxy)methyl]benzonitrile | 889118-14-3

• 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: 3-[(4-hydroxymethylphenyl)-(tetrahydropyran-2-yloxy)methyl]benzonitrile
• 英文别名: 3-{(S)-[4-(Hydroxymethyl)phenyl][(oxan-2-yl)oxy]methyl}benzonitrile；3-[(S)-[4-(hydroxymethyl)phenyl]-(oxan-2-yloxy)methyl]benzonitrile
• CAS: 889118-14-3
• 化学式: C₂₀H₂₁NO₃
• 分子量: 323.392
• InChiKey: RSKYMAVGNXGDKQ-ANYOKISRSA-N

物化性质

• 沸点：
  498.5±45.0 °C(Predicted)
• 密度：
  1.21±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  62.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2,4-二羟基-3-丙基苯乙酮 、 3-[(4-hydroxymethylphenyl)-(tetrahydropyran-2-yloxy)methyl]benzonitrile 在 甲基磺酰氯 、 三乙胺 、 potassium carbonate 、 sodium iodide 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 反应 27.0h， 以100%的产率得到3-[[4-(4-acetyl-3-hydroxy-2-propyl-phenoxymethyl)phenyl](tetrahydropyran-2-yloxy)methyl]benzonitrile
  参考文献：
  名称：

  Optimized Catalytic Enantioselective Aryl Transfer Process Gives Access to mGlu2 Receptor Potentiators

  摘要：

  An asymmetric enantioselective aryl transfer reaction was developed to give access to the diarylmethanol 7 and ultimately acetate 2 which is useful for the preparation of mGlu2 receptor potentiators ( Scheme 3). The aryl transfer chemistry involved the preparation of a proposed arylalkylzinc species 14 from boroxine 16 and diethylzinc (DEZ), and reacting this mixture with aldehyde 5 in the presence of chiral ligand 15. During the course of optimizing the preparations of proposed intermediate 14 and diarylmethanol 7, an understanding of optimal stoichiometry and reaction times was gained through empirical observation, the use of solution IR, and analyzing off-gases via real time gas analysis/mass spectroscopy. The preparation of diarylmethanol 7 and subsequent conversion into acetate 2 required carefully selected workups, selective extractions, and azeotropic distillations to generate a series of stock solutions to accommodate oil intermediates that finally gave acetate 2 as a crystalline solid with > 99% ee.

  DOI：

  10.1021/op0602268
• 作为产物：
  描述：

  1-溴-4-叔丁基二甲基硅烷氧甲基苯 在 四丁基氟化铵 、 4-甲基苯磺酸吡啶 、 magnesium 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 正庚烷 、 二氯甲烷 、 1,2-二溴乙烷 为溶剂， 反应 44.36h， 生成 3-[(4-hydroxymethylphenyl)-(tetrahydropyran-2-yloxy)methyl]benzonitrile
  参考文献：
  名称：

  Optimized Catalytic Enantioselective Aryl Transfer Process Gives Access to mGlu2 Receptor Potentiators

  摘要：

  An asymmetric enantioselective aryl transfer reaction was developed to give access to the diarylmethanol 7 and ultimately acetate 2 which is useful for the preparation of mGlu2 receptor potentiators ( Scheme 3). The aryl transfer chemistry involved the preparation of a proposed arylalkylzinc species 14 from boroxine 16 and diethylzinc (DEZ), and reacting this mixture with aldehyde 5 in the presence of chiral ligand 15. During the course of optimizing the preparations of proposed intermediate 14 and diarylmethanol 7, an understanding of optimal stoichiometry and reaction times was gained through empirical observation, the use of solution IR, and analyzing off-gases via real time gas analysis/mass spectroscopy. The preparation of diarylmethanol 7 and subsequent conversion into acetate 2 required carefully selected workups, selective extractions, and azeotropic distillations to generate a series of stock solutions to accommodate oil intermediates that finally gave acetate 2 as a crystalline solid with > 99% ee.

  DOI：

  10.1021/op0602268

文献信息

• Potentiators Of Glutamate Receptors
  申请人：AICHER Thomas Daniel

  公开号：US20090318481A1

  公开（公告）日：2009-12-24

  This application relates to a substituted hydroxyphenyl ketone compound of formula I, or a pharmaceutically acceptable salt thereof, a pharmaceutical composition thereof and its use in treating migraine. This application also relates to processes for preparing a compound of formula I, and intermediate compounds useful therein.

  本申请涉及一种公式I的取代羟基苯酮化合物，或其药学上可接受的盐，及其在治疗偏头痛中的应用，以及制备公式I化合物的过程和其中有用的中间体化合物的应用。
• Potentiators of glutamate receptors
  申请人：Eli Lilly and Company

  公开号：US07803938B2

  公开（公告）日：2010-09-28

  This application relates to a substituted hydroxyphenyl ketone compound of formula I, or a pharmaceutically acceptable salt thereof, a pharmaceutical composition thereof and its use in treating migraine. This application also relates to processes for preparing a compound of formula I, and intermediate compounds useful therein.

  本申请涉及一种I式置换羟基苯酮化合物，或其药学上可接受的盐，以及其在治疗偏头痛中的应用的制药组合物。本申请还涉及制备I式化合物的过程以及其中有用的中间体化合物。
• US7598423B2
  申请人：——

  公开号：US7598423B2

  公开（公告）日：2009-10-06
• US7816523B2
  申请人：——

  公开号：US7816523B2

  公开（公告）日：2010-10-19
• US7803938B2
  申请人：——

  公开号：US7803938B2

  公开（公告）日：2010-09-28