(2R)-2-acetoxy-2-phenyl-acetic acid;(3R,4R)-1-benzyl-4-(benzylamino)piperidin-3-ol | 1384733-04-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (2R)-2-acetoxy-2-phenyl-acetic acid;(3R,4R)-1-benzyl-4-(benzylamino)piperidin-3-ol
• 英文别名: (2R)-2-acetyloxy-2-phenylacetic acid;(3R,4R)-1-benzyl-4-(benzylamino)piperidin-3-ol
• CAS: 1384733-04-3
• 化学式: C₁₀H₁₀O₄*C₁₉H₂₄N₂O
• 分子量: 490.599
• InChiKey: JLVAXYQSPURDON-WEIRHIGXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.79
• 重原子数：
  36
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  99.1
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2R)-2-acetoxy-2-phenyl-acetic acid;(3R,4R)-1-benzyl-4-(benzylamino)piperidin-3-ol 在 sodium hydroxide 作用下， 以 甲基叔丁基醚 、 水 为溶剂， 以93%的产率得到(3RS,4RS)-1-benzyl-4-(benzylamino)piperidin-3-ol
  参考文献：
  名称：

  Selection and Scale-Up Evaluation of an Alternative Route to (−)-(3R,4R)-1-Benzyl-4-(benzylamino)piperidin-3-ol

  摘要：

  An efficient, scalable synthesis of (-)-(3R,4R)-1-benzyl-4-(benzylamino)piperidin-3-ol (4) is described. Reduction of the pyridinium salt prepared from pyridine and benzyl chloride generated the corresponding tetrahydropyridine derivative. A two-stage epoxidation, followed by ring-opening of the epoxide with BnNH2, established the regiochemistry of the amino alcohol and served to set the trans-relationship between the amine and the hydroxyl group. The resulting racemic intermediate was then resolved by salt formation with (R)-O-acetyl mandelic acid. The process produced the O-acetyl mandelic acid salt of (-)-4 in 27% overall yield from benzyl chloride.

  DOI：

  10.1021/op300174w
• 作为产物：
  描述：

  氯化苄 在 N-氯代丁二酰亚胺 、 三氟乙酸 、 lithium chloride 作用下， 以 乙醇 、 甲基叔丁基醚 、 水 、 乙腈 、 正丁醇 为溶剂， -10.0~85.0 ℃ 、13.33 kPa 条件下， 反应 42.33h， 生成 (2R)-2-acetoxy-2-phenyl-acetic acid;(3R,4R)-1-benzyl-4-(benzylamino)piperidin-3-ol
  参考文献：
  名称：

  Selection and Scale-Up Evaluation of an Alternative Route to (−)-(3R,4R)-1-Benzyl-4-(benzylamino)piperidin-3-ol

  摘要：

  An efficient, scalable synthesis of (-)-(3R,4R)-1-benzyl-4-(benzylamino)piperidin-3-ol (4) is described. Reduction of the pyridinium salt prepared from pyridine and benzyl chloride generated the corresponding tetrahydropyridine derivative. A two-stage epoxidation, followed by ring-opening of the epoxide with BnNH2, established the regiochemistry of the amino alcohol and served to set the trans-relationship between the amine and the hydroxyl group. The resulting racemic intermediate was then resolved by salt formation with (R)-O-acetyl mandelic acid. The process produced the O-acetyl mandelic acid salt of (-)-4 in 27% overall yield from benzyl chloride.

  DOI：

  10.1021/op300174w

文献信息

• Synthetic approaches to a chiral 4-amino-3-hydroxy piperidine with pharmaceutical relevance
  作者：Adrian Ortiz、Ian S. Young、James R. Sawyer、Yi Hsiao、Amarjit Singh、Masano Sugiyama、R. Michael Corbett、Melissa Chau、Zhongping Shi、David A. Conlon

  DOI：10.1039/c2ob25411e

  日期：——

  strategies were evaluated towards the preparation of (−)-(3R,4R)-1-benzyl-4-(benzylamino)piperidin-3-ol (1), which was constructed with control over the relative and absolute stereochemistry of the 4,3-amino alcohol moiety. The first strategy employed a novel RhI catalyzed asymmetric hydrogenation, while two other strategies exploited the existing stereochemistry in 2-deoxy-D-ribose, and the fourth explored

  评估了四种综合策略来制备甲壳素。 （-）-（3 R，4 R）-1-苄基-4-（苄基氨基）哌啶-3-醇（1），其是通过控制4，3-氨基醇部分的相对和绝对立体化学而构建的。第一种策略采用了新型的Rh I催化的不对称氢化反应，而另外两种策略则采用了现有的立体化学方法。2-脱氧-D-核糖，和第四次探索生物催化和古典拆分技术作为一种手段赋予对映体中间体途径到目标结构（-）- 1对映体富集。