(3RS,4RS)-1-benzyl-4-(benzylamino)piperidin-3-ol

• 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: (3RS,4RS)-1-benzyl-4-(benzylamino)piperidin-3-ol
• 英文别名: trans-1-benzyl-4-benzylaminopiperidin-3-ol；(3R,4R)-1-Benzyl-4-(benzylamino)piperidin-3-OL
• 化学式: C₁₉H₂₄N₂O
• 分子量: 296.412
• InChiKey: HUVGDTRCZVNHGX-RTBURBONSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  35.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (3RS,4RS)-1-benzyl-4-(benzylamino)piperidin-3-ol 在 氢气 、 palladium(II) hydroxide 、 三乙胺 、 potassium hydroxide 作用下， 以 N-甲基吡咯烷酮 、 乙醇 、 异丁醇 、 水 、 异丙醇 、 甲苯 为溶剂， 20.0~75.0 ℃ 、308.18 kPa 条件下， 反应 4.5h， 生成 (3R,4R)-4-氨基-1-[[4-[(3-甲氧基苯基)氨基]吡咯并[2,1-f][1,2,4]三嗪-5-基]甲基]哌啶-3-醇
  参考文献：
  名称：

  Evolution of the Process for the Preparation of a Selective ErbB VEGF Receptor Inhibitor

  摘要：

  An efficient synthetic route to the potent and selective ErbB VEGF receptor inhibitor, BMS-690514 (1) is described. Strategic modifications in both approach and procedure addressed several issues, which led to a safe, efficient, and economical process for the preparation of multi-kilogram quantities of 1. The convergent route involves alkylation of a suitably protected (3R,4R)-4-aminopiperidin-3-ol with the triethyl(alkyl) ammonium salt of a functionalized pyrrolotriazine 3a followed by deprotection to provide 1 as the crystalline free base.

  DOI：

  10.1055/s-0032-1317540
• 作为产物：
  描述：

  1,2,3,6-四氢-1-(苯基甲基)吡啶 在 N-氯代丁二酰亚胺 、 三氟乙酸 、 potassium hydroxide 作用下， 以 甲基叔丁基醚 、 水 、 丙酮 为溶剂， 反应 33.58h， 生成 (3RS,4RS)-1-benzyl-4-(benzylamino)piperidin-3-ol
  参考文献：
  名称：

  合成方法以手性4-氨基-3-羟基哌啶由药物关联†

  摘要：

  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。

  DOI：

  10.1039/c2ob25411e

文献信息

• PROCESS FOR PRODUCING 1-SUBSTITUTED TRANS-4-(SUBSTITUTED AMINO) PIPERIDIN-3-OL
  申请人：Aikawa Toshiaki

  公开号：US20110172431A1

  公开（公告）日：2011-07-14

  A process is provided for producing a 1-substituted trans-4-(substituted amino)piperidin-3-ol represented by formula (III-1): The process includes a step of reacting a 1-substituted-3,4-epoxypiperidine represented by formula (I): with an amine compound represented by formula (II) in the presence of an inorganic lithium salt. By utilizing the process, trans-4-aminopiperidin-3-ol compounds useful as various chemical products, such as medicine intermediates, can be produced.

  提供了一种生产1-取代的反式-4-(取代氨基)哌啶-3-醇的过程，其化学式为(III-1)：该过程包括以下步骤：将一种化学式为(I)的1-取代-3,4-环氧哌啶与一种化学式为(II)的胺化合物在无机锂盐存在下反应。通过利用该过程，可以生产用途广泛的反式-4-氨基哌啶-3-醇化合物，如药物中间体等化学产品。
• Remarkable switch of regioselectivity in epoxide ring opening of 3-benzyl-7-oxa-3-azabicyclo[4.1.0]heptane with amines: practical synthesis of trans-4-amino-3-hydroxypiperidines and trans-3-amino-4-hydroxypiperidines
  作者：Osamu Tokuda、Toshiaki Aikawa、Tetsuya Ikemoto、Isao Kurimoto

  DOI：10.1016/j.tetlet.2010.03.061

  日期：2010.5

  A simple and highly C3 selective ring-opening method for 3,4-epoxypiperidines has been developed. We also describe a practical improvement of the C4 selective ring-opening method using the same N-alkyl substituted 3,4-epoxypiperidines. This method provides access to pharmaceutically relevant trans-3-amino-4-hydroxypiperidines and trans-4-amino-3-hydroxypiperidines with simple procedures.

  已经开发出一种简单且高度C3的3,4-环氧哌啶选择性开环方法。我们还描述了使用相同的N-烷基取代的3，4-环氧哌啶对C4选择性开环方法的实际改进。该方法提供了以简单的方法获得药学上相关的反式-3-氨基-4-羟基哌啶和反式-4-氨基-3-羟基哌啶的方法。
• PROCESS FOR PRODUCING 1-SUBSTITUTED TRANS-4-(SUBSTITUTED AMINO)PIPERIDIN-3-OL
  申请人：Sumitomo Chemical Company, Limited

  公开号：EP2351738A1

  公开（公告）日：2011-08-03

  A process for producing a 1-substituted trans-4-(substituted amino)piperidin-3-ol represented by formula (III-1): wherein R1 represents an aromatic carbocyclic group, an alkyl group having 1 to 12 carbon atoms which may be substituted with one or more aromatic carbocyclic groups, an alkenyl group having 2 to 14 carbon atoms which may be substituted with one or more aromatic carbocyclic groups, or an alkynyl group having 2 to 12 carbon atoms which may be substituted with one or more aromatic carbocyclic groups, and the like, which comprises a step of reacting a 1-substituted-3,4-epoxypiperidine represented by formula (I): with an amine compound represented by formula (II) in the presence of an inorganic lithium salt. By utilizing the process, trans-4-aminopiperidin-3-ol compounds useful as various chemical products, such as medicine intermediates, can be produced.

  一种生产式 (III-1) 所代表的 1-取代反式-4-(取代氨基)哌啶-3-醇的工艺： 其中 R1 代表芳香族碳环基团、具有 1 至 12 个碳原子且可被一个或多个芳香族碳环基团取代的烷基、具有 2 至 14 个碳原子且可被一个或多个芳香族碳环基团取代的烯基、或具有 2 至 12 个碳原子且可被一个或多个芳香族碳环基团取代的炔基等、 其中包括使式（I）代表的 1-取代-3,4-环氧哌啶反应的步骤： 与式 (II) 所代表的胺化合物反应 在无机锂盐存在下进行。利用该工艺可生产出反式-4-氨基哌啶-3-醇化合物，该化合物可用作各种化学产品，如医药中间体。
• [EN] INHIBITORS OF BRUTON'S TYROSINE KINASE<br/>[FR] INHIBITEURS DE LA TYROSINE KINASE DE BRUTON
  申请人：BIOGEN IDEC INC

  公开号：WO2013185082A3

  公开（公告）日：2014-04-03
• Selection and Scale-Up Evaluation of an Alternative Route to (−)-(3<i>R</i>,4<i>R</i>)-1-Benzyl-4-(benzylamino)piperidin-3-ol
  作者：Ian S. Young、Adrian Ortiz、James R. Sawyer、David A. Conlon、Frederic G. Buono、Simon W. Leung、Justin L. Burt、Eric W. Sortore

  DOI：10.1021/op300174w

  日期：2012.9.21

  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.