1-((R)-6-Bromo-1,2,3,4-tetrahydro-naphthalen-2-yl)-piperidin-4-one | 167172-96-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: 1-((R)-6-Bromo-1,2,3,4-tetrahydro-naphthalen-2-yl)-piperidin-4-one
• 英文别名: 1-[(2R)-6-bromo-1,2,3,4-tetrahydronaphthalen-2-yl]piperidin-4-one
• CAS: 167172-96-5
• 化学式: C₁₅H₁₈BrNO
• 分子量: 308.218
• InChiKey: YKEIOVRMPAPIBV-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  氰化锌 、 1-((R)-6-Bromo-1,2,3,4-tetrahydro-naphthalen-2-yl)-piperidin-4-one 在 palladium diacetate diethylzinc 、 三(邻甲基苯基)磷 作用下， 以 正己烷 为溶剂， 反应 1.5h， 以80%的产率得到(R)-5,6,7,8-Tetrahydro-6-(4-oxopiperidin-1-yl)-2-naphthalenecarbonitrile
  参考文献：
  名称：

  Asymmetric Synthesis of MK-0499

  摘要：

  Described herein is an efficient asymmetric synthesis of the potent antiarrhthymia agent MK-0499. The route is convergent and is highlighted by two stereoselective reactions. A ruthenium-catalyzed, enantioselective hydrogenation of an enamide was developed for the preparation of the key amine intermediate. Oxazaborolidine-mediated ketone reduction was utilized to establish the alcohol stereochemistry. Optimization of this chemistry led to an IPA modified reduction method which provides enhanced stereoselectivity.

  DOI：

  10.1021/jo00119a008
• 作为产物：
  描述：

  1-乙基-1-甲基-4-氧代哌啶-1-碘化物 、 2-Amino-6-bromo tetralin 在 potassium carbonate 作用下， 以 乙醇 为溶剂， 反应 0.75h， 以87%的产率得到1-((R)-6-Bromo-1,2,3,4-tetrahydro-naphthalen-2-yl)-piperidin-4-one
  参考文献：
  名称：

  Asymmetric Synthesis of MK-0499

  摘要：

  Described herein is an efficient asymmetric synthesis of the potent antiarrhthymia agent MK-0499. The route is convergent and is highlighted by two stereoselective reactions. A ruthenium-catalyzed, enantioselective hydrogenation of an enamide was developed for the preparation of the key amine intermediate. Oxazaborolidine-mediated ketone reduction was utilized to establish the alcohol stereochemistry. Optimization of this chemistry led to an IPA modified reduction method which provides enhanced stereoselectivity.

  DOI：

  10.1021/jo00119a008

文献信息

• Asymmetric Synthesis of MK-0499
  作者：David M. Tschaen、Lee Abramson、Dongwei Cai、Richard Desmond、Ulf-H. Dolling、Lisa Frey、Sandor Karady、Yao-Jun Shi、Thomas R. Verhoeven

  DOI：10.1021/jo00119a008

  日期：1995.7

  Described herein is an efficient asymmetric synthesis of the potent antiarrhthymia agent MK-0499. The route is convergent and is highlighted by two stereoselective reactions. A ruthenium-catalyzed, enantioselective hydrogenation of an enamide was developed for the preparation of the key amine intermediate. Oxazaborolidine-mediated ketone reduction was utilized to establish the alcohol stereochemistry. Optimization of this chemistry led to an IPA modified reduction method which provides enhanced stereoselectivity.