ethyl (R)-5-methyl-3-oxo-octanoate | 874208-98-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 酮酸及其衍生物
• 英文名称: ethyl (R)-5-methyl-3-oxo-octanoate
• 英文别名: ethyl (R)-5-methyl-3-oxooctanoate；ethyl (5R)-5-methyl-3-oxooctanoate
• CAS: 874208-98-7
• 化学式: C₁₁H₂₀O₃
• 分子量: 200.278
• InChiKey: JXCGCJXWILMTQF-SECBINFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  14
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl (R)-5-methyl-3-oxo-octanoate 在 氨 作用下， 以 乙醇 为溶剂， 生成 ethyl (5R)-3-amino-5-methyloct-2-enoate
  参考文献：
  名称：

  通过非对称酰胺氢化作为α2δ配体的非对映选择性，大规模合成β-氨基酸，用于治疗广泛性焦虑症和失眠

  摘要：

  β-氨基酸1和2的合成是通过前一篇文章中报道的不对称Michael加成路线的替代路线来实现的。这两种化合物均与钙通道的α2δ亚基结合并具有重要的医学应用，它们是通过一种新方法在中试工厂中以千克级规模制备的，该新方法通过烯酰胺的不对称加氢在β-碳原子上引入手性。前体。发现两种基于Rh的催化剂（R）-mTCFP-Rh（COD）BF 4和（R）-binapine-Rh（COD）BF 4在此转化过程中具有较高的非对映选择性。描述了用于催化剂选择的方法开发。

  DOI：

  10.1016/j.tetlet.2009.08.111
• 作为产物：
  描述：

  (3R,4R,5S)-4-methyl-3-(3-methyl-hexanoyl)-5-phenyl-oxazolidin-2-one 、 ethyl potassium malonate 在 三乙胺 、 magnesium chloride 、 盐酸 作用下， 以 乙腈 、 水 为溶剂， 生成 ethyl (R)-5-methyl-3-oxo-octanoate
  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

• Expeditious, large scale preparation of ethyl (R)-5-methyl-3-oxo octanoate via a cross Claisen reaction between N-acyl oxazolidinone derivatives and the magnesium enolate of potassium ethyl malonate
  作者：Javier Magano、Thomas N. Nanninga、Derick D. Winkle

  DOI：10.1016/j.tetlet.2008.03.004

  日期：2008.4

  A new and efficient method for the direct conversion of N-acyl oxazolidinones to a β-keto ester is disclosed. The one-pot transformation is effected by the utilization of an excess of Lewis acid along with base and potassium ethyl malonate. This methodology has been applied to the large scale preparation of ethyl (R)-5-methyl-3-oxooctanoate.

  公开了一种新的有效的方法，用于将N-酰基恶唑烷酮直接转化为β-酮酯。一锅转化是通过利用过量的路易斯酸以及碱和丙二酸钾钾来实现的。该方法已经应用于大规模制备（R）-5-甲基-3-氧辛酸乙酯。
• 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。
• The Development of a Practical Multikilogram Synthesis of the Chiral β-Amino Acid Imagabalin Hydrochloride (PD-0332334) via Asymmetric Hydrogenation
  作者：Melissa Birch、Stephen Challenger、Jean-Philippe Crochard、David Fradet、Hayley Jackman、Amy Luan、Evelyn Madigan、Neil McDowall、Kevin Meldrum、Charles M. Gordon、Magnus Widegren、Stephen Yeo

  DOI：10.1021/op2001639

  日期：2011.9.16

  The development and implementation of a robust process for the manufacture of metric ton quantities of the alpha 2 delta ligand imagabalin hydrochloride 4 is described. Key aspects of the synthesis include a chromatography-free, two-step telescoped process to prepare a mixture of Z:E-enamides 7 followed by a robust asymmetric hydrogenation with the rhodium-trichickenfootphos catalyst 8 to install the (3S)-stereocentre. Hydrolysis of the acetarnide and ester protecting groups in the final step followed by isolation and recrystallisation of the hydrochloride salt gave high purity 4 in 40-50% overall yields.
• [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.
• [EN] PREPARATION OF BETA-AMINO ACID PRECURSORS VIA INDIUM (III) MEDIATED MARKOVNIKOV ADDITION AND KNOEVENAGEL CONDENSATION<br/>[FR] PREPARATION DE PRECURSEURS DE BETA-AMINOACIDE PAR ADDITION DE MARKOVNIKOV ET CONDENSATION DE KNOEVENAGEL A MEDIATION ASSUREE PAR DE L'INDIUM (III)
  申请人：WARNER LAMBERT CO

  公开号：WO2006100606A2

  公开（公告）日：2006-09-28

  (EN) Disclosed are materials and methods for preparing precursors of optically active &bgr;-amino acids, which bind to the alpha-2-delta (&agr;2&dgr;) subunit of a calcium channel and are useful for treating pain, fibromyalgia, and a variety of psychiatric and sleep disorders. The method includes reacting a malonate derivative with a terminal alkyne in the presence of an In(III) catalyst.(FR) L'invention concerne des matériaux et des procédés pour la préparation de précurseurs de ß-aminoacides optiquement actifs, qui se lient à la sous-unité alpha-2-delta (a2d) d'un canal calcique et qui sont utiles pour le traitement de la douleur, de la fibromyalgie, et de divers troubles psychiatriques ou du sommeil. Le procédé de l'invention consiste à faire réagir un dérivé de malonate avec un alcyne terminal en présence d'un catalyseur In(III).