(E)-3-methyl-5-(4-methylpent-1-enyl)-4-nitroisoxazole | 1541042-34-5

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 英文名称: (E)-3-methyl-5-(4-methylpent-1-enyl)-4-nitroisoxazole
• 英文别名: 3-methyl-5-[(E)-4-methylpent-1-enyl]-4-nitro-1,2-oxazole
• CAS: 1541042-34-5
• 化学式: C₁₀H₁₄N₂O₃
• 分子量: 210.233
• InChiKey: QORSIPGEKMNCMG-GQCTYLIASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  71.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (E)-3-methyl-5-(4-methylpent-1-enyl)-4-nitroisoxazole 在 potassium carbonate 、 sodium hydroxide 、 N-苄基溴化金鸡纳碱 作用下， 以 水 、 甲苯 为溶剂， 反应 92.0h， 生成 (S)-5-methyl-3-(nitromethyl)hexanoic acid
  参考文献：
  名称：

  Development and Scale-up of an Organocatalytic Enantioselective Process to Manufacture (S)-Pregabalin

  摘要：

  Herein is reported the development of a new process to manufacture (S)-pregabalin. The method comprises six steps, run under the catalysis of a recyclable polymer bound phase transfer catalyst, and afforded (S)-pregabalin in overall 54% yield, starting from building blocks acetylacetone, isovaleraldehyde, and nitromethane.

  DOI：

  10.1021/acs.oprd.5b00160
• 作为产物：
  描述：

  3,5-二甲基异唑 在 硫酸 、 硝酸 、 甲基磺酰氯 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 27.17h， 生成 (E)-3-methyl-5-(4-methylpent-1-enyl)-4-nitroisoxazole
  参考文献：
  名称：

  Development and Scale-up of an Organocatalytic Enantioselective Process to Manufacture (S)-Pregabalin

  摘要：

  Herein is reported the development of a new process to manufacture (S)-pregabalin. The method comprises six steps, run under the catalysis of a recyclable polymer bound phase transfer catalyst, and afforded (S)-pregabalin in overall 54% yield, starting from building blocks acetylacetone, isovaleraldehyde, and nitromethane.

  DOI：

  10.1021/acs.oprd.5b00160

文献信息

• An improved procedure to prepare 3-methyl-4-nitroalkylenethylisoxazoles and their reaction under catalytic enantioselective Michael addition with nitromethane
  作者：Maria Moccia、Robert J. Wells、Mauro. F. A. Adamo

  DOI：10.1039/c4ob02109f

  日期：——

  Herein, we describe a short synthesis of 3-methyl-4-nitro-5-alkylethenyl isoxazoles and their reactivity as Michael acceptors. The title compounds reacted with nitromethane under phase-transfer catalysis to provide highly enantioenriched adducts (up to 93% ee) which were then converted to the corresponding γ-nitroacids.

  在这里，我们描述了3-甲基-4-硝基-5-烷基乙烯基异恶唑的简短合成及其作为迈克尔受体的反应性。在相转移催化下，标题化合物与硝基甲烷反应，得到高度对映体富集的加合物（最高93％ee），然后将其转化为相应的γ-硝酸。
• Preparation and reactivity of sterically encumbered organocatalysts and their use in the preparation of ( S )-Pregabalin precursors
  作者：Mauro Cortigiani、Alberto Tampieri、Claudio Monasterolo、Andrea Mereu、Mauro F.A. Adamo

  DOI：10.1016/j.tetlet.2017.09.067

  日期：2017.11

  Herein we describe the preparation of a new class of sterically demanding organocatalysts derived from d-fructose and their use, alongside hitherto unreported doubly quaternarised Cinchona ammonium salts, in the Michael reaction of nitromethane with 4-nitro-5-alkenyl-isoxazoles.

  本文中，我们描述了一种新型的衍生自d-果糖的新型空间需求有机催化剂的制备及其在迄今为止从未报道过的双季铵化金鸡纳铵盐的使用中，在硝基甲烷与4-硝基-5-烯基-异恶唑的迈克尔反应中的应用。
• [EN] PROCESS FOR THE PREPARATION OF GAMMA AMINO ACIDS AND INTERMEDIATES USED IN SAID PROCESS<br/>[FR] PROCÉDÉ DE PRÉPARATION DE ACIDES AMINÉS GAMMA ET INTERMÉDIAIRES UTILISÉS DANS CE PROCÉDÉ
  申请人：ROYAL COLLEGE OF SURGEONS IE

  公开号：WO2013076225A1

  公开（公告）日：2013-05-30

  The invention relates to the preparation of gamma amino acids of formula (I) and pharmaceutically acceptable salts, solvates and prodrugs thereof, and to intermediates used for their preparation. (formula I) wherein R1 is selected from an alkyl group, an alkenyl group, an alkynyl group and a cycloalkyl group, each of which may be optionally substituted and * denotes a chiral centre. In particular, the present invention provides an efficient synthesis of (S)-pregabalin which is suitable for carrying out on an industrial scale.

  该发明涉及制备公式(I)的γ-氨基酸及其药学上可接受的盐、溶剂合物和前药，以及用于其制备的中间体。(公式I)其中R1选自烷基、烯基、炔基和环烷基，每种基团均可选择性地被取代，*表示一个手性中心。特别是，本发明提供了(S)-普瑞巴林的高效合成方法，适用于工业规模生产。
• Catalytic enantioselective addition of isocyanoacetate to 3-methyl-4-nitro-5-styrylisoxazoles under phase transfer catalysis conditions
  作者：Paolo Disetti、Maria Moccia、Diana Salazar Illera、Surisetti Suresh、Mauro F. A. Adamo

  DOI：10.1039/c5ob01880c

  日期：——

  The reaction between 3-methyl-4-nitro-5-styrylisoxazoles and ethyl isocyanoacetate proceeded under phase transfer catalysis to give enantioenriched monoadducts in high enantiomeric excess (up to 99% ee). The resulting adducts were subsequently cyclised to give 2,3-dihydropyrroles and substituted pyrrolidines in identical high ees and as a single diastereoisomer.

  3-甲基-4-硝基-5-苯乙烯基恶唑与异氰基乙酸乙酯之间的反应在相转移催化下进行，得到高对映体过量（至多99％ee）的对映体富集的单加合物。随后将所得的加合物环化，以相同的高ee和单个非对映异构体形式得到2，3-二氢吡咯和取代的吡咯烷。
• PROCESS FOR THE PREPARATION OF GAMMA AMINO ACIDS AND INTERMEDIATES USED IN SAID PROCESS
  申请人：Royal College of Surgeons in Ireland

  公开号：US20140336412A1

  公开（公告）日：2014-11-13

  The invention relates to the preparation of gamma amino acids of formula (I) and pharmaceutically acceptable salts, solvates and prodrugs thereof, and to intermediates used for their preparation. (formula I) wherein R 1 is selected from an alkyl group, an alkenyl group, an alkynyl group and a cycloalkyl group, each of which may be optionally substituted and * denotes a chiral centre. In particular, the present invention provides an efficient synthesis of (S)-pregabalin which is suitable for carrying out on an industrial scale.

  本发明涉及制备公式(I)的γ-氨基酸及其药学上可接受的盐、溶剂化物和前药，以及用于它们制备的中间体。(公式I)其中R1选自烷基、烯基、炔基和环烷基，每个基团均可选择性地被取代，*表示手性中心。特别地，本发明提供了一种适用于工业规模的(S)-pregabalin的高效合成方法。