ethyl (5R)-3-hydroxy-5-methyloctanoate | 874209-38-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: ethyl (5R)-3-hydroxy-5-methyloctanoate
• CAS: 874209-38-8
• 化学式: C₁₁H₂₂O₃
• 分子量: 202.294
• InChiKey: ASZRNFBOFVPOPX-YHMJZVADSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  14
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl (5R)-3-hydroxy-5-methyloctanoate 、 甲基磺酰氯 以 乙酸乙酯 为溶剂， 生成 ethyl (5R)-5-methyl-3-methylsulfonyloxyoctanoate
  参考文献：
  名称：

  Diastereoselective, large-scale synthesis of β-amino acids via asymmetric aza-Michael addition as α2δ ligands for the treatment of generalized anxiety disorder and insomnia

  摘要：

  Scalable synthetic routes to beta-amino acids 1 and 2 are presented. These two compounds, which bind to the alpha 2 delta subunit of calcium channels and have important medical applications, have been prepared on kilogram scale in our pilot plant through an improved synthesis that avoids the use of highly toxic reagents and hazardous chemistry present in the original Medicinal Chemistry route. The two chiral centers are introduced through asymmetric Michael and aza-Michael reactions with excellent diastereoselectivity. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2009.08.119
• 作为产物：
  描述：

  ethyl (R)-5-methyl-3-oxo-octanoate 在 tris(triphenylphosphine)ruthenium(II) chloride 、 硫酸 、 氢气 作用下， 以 乙醇 为溶剂， 60.0 ℃ 、344.75 kPa 条件下， 生成 ethyl (5R)-3-hydroxy-5-methyloctanoate
  参考文献：
  名称：

  Diastereoselective, large-scale synthesis of β-amino acids via asymmetric aza-Michael addition as α2δ ligands for the treatment of generalized anxiety disorder and insomnia

  摘要：

  Scalable synthetic routes to beta-amino acids 1 and 2 are presented. These two compounds, which bind to the alpha 2 delta subunit of calcium channels and have important medical applications, have been prepared on kilogram scale in our pilot plant through an improved synthesis that avoids the use of highly toxic reagents and hazardous chemistry present in the original Medicinal Chemistry route. The two chiral centers are introduced through asymmetric Michael and aza-Michael reactions with excellent diastereoselectivity. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2009.08.119

文献信息

• A Simplified Process for the Manufacture of Imagabalin Hydrochloride (PD-0332334), an α2δ-Ligand for the Treatment of Generalised Anxiety Disorder
  作者：Melissa Birch、Stephen Challenger、Jean-Philippe Crochard、David Fradet、Hayley Jackman、Amy Luan、Evelyn Madigan、Jinu S. Mathew、Neil McDowall、Kevin Meldrum、Charles M. Gordon、Philip Peach、Stephen Yeo

  DOI：10.1021/op2002326

  日期：2011.11.18

  The development of a highly efficient two-step process for the manufacture of the α2δ-ligand imagabalin hydrochloride 1 is described in 50% overall yield from (R)-3-methylhexanoic acid 2. Key aspects of this route include the development of a one-pot process for the synthesis of β-enamine ester 7 and its subsequent diastereoselective hydrogenation with a Ru-(S)-BINAP catalyst. The use of a combination

  描述了以（R）-3-甲基己酸2的总收率为50％的高效生产两步法生产α2δ-配体伊马巴林盐酸盐1的过程。该路线的关键方面包括开发一锅法合成β-烯胺酯7以及随后用Ru-（S）-BINAP催化剂进行非对映选择性氢化。在这种不对称的氢化反应中，TFA，三氟乙酸铵和相对较低的压力的组合使用是新的条件。与先前描述的启用路线相比，所描述的简化过程实现了4倍的商品成本降低。
• PREPARATION OF BETA-AMINO ACIDS HAVING AFFINITY FOR THE ALPHA-2-DELTA PROTEIN
  申请人：Conway Brian G

  公开号：US20090247743A1

  公开（公告）日：2009-10-01

  Disclosed are materials and methods for preparing optically active β-amino acids of Formula 1, which bind to the alpha-2-delta (α2δ) subunit of a calcium channel.

  本发明涉及制备配方1的光学活性β-氨基酸的材料和方法，该配方1结合到钙通道的α2δ亚单位。
• [EN] PREPARATION OF BETA-AMINO ACIDS HAVING AFFINITY FOR THE ALPHA-2-DELTA PROTEIN<br/>[FR] PREPARATION DE BETA-AMINOACIDES AYANT UNE AFFINITE POUR LA PROTEINE ALPHA-2-DELTA
  申请人：WARNER LAMBERT CO

  公开号：WO2006008612A2

  公开（公告）日：2006-01-26

  Disclosed are materials and methods for preparing optically active ß-amino acids of Formula (1), which bind to the alpha-2-delta (α2δ) subunit of a calcium channel.
• Diastereoselective, large-scale synthesis of β-amino acids via asymmetric aza-Michael addition as α2δ ligands for the treatment of generalized anxiety disorder and insomnia
  作者：Javier Magano、Daniel Bowles、Brian Conway、Thomas N. Nanninga、Derick D. Winkle

  DOI：10.1016/j.tetlet.2009.08.119

  日期：2009.11

  Scalable synthetic routes to beta-amino acids 1 and 2 are presented. These two compounds, which bind to the alpha 2 delta subunit of calcium channels and have important medical applications, have been prepared on kilogram scale in our pilot plant through an improved synthesis that avoids the use of highly toxic reagents and hazardous chemistry present in the original Medicinal Chemistry route. The two chiral centers are introduced through asymmetric Michael and aza-Michael reactions with excellent diastereoselectivity. (C) 2009 Elsevier Ltd. All rights reserved.