(2S,3s)-1-n-苄基-3-羟基-2-苯基哌啶 | 250589-64-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: (2S,3s)-1-n-苄基-3-羟基-2-苯基哌啶
• 英文名称: (2S,3S)-1-benzyl-3-hydroxy-2-phenylpiperidin
• 英文别名: (2S,3R)-1-benzyl-2-phenylpiperidin-3-ol；(2S,3S)-1-benzyl-2-phenyl-3-piperidinol；(2S,3S)-1-benzyl-2-phenylpiperidin-3-ol
• CAS: 250589-64-1
• 化学式: C₁₈H₂₁NO
• 分子量: 267.371
• InChiKey: FPHQSHFUYFORCS-ROUUACIJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  23.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (2S,3s)-1-n-苄基-3-羟基-2-苯基哌啶 在 palladium dihydroxide 氢气 作用下， 以 甲醇 为溶剂， 反应 13.0h， 以90%的产率得到cis-(3S)-hydroxy-(2S)-phenylpiperidine
  参考文献：
  名称：

  A Novel and Highly Regioselective Approach to 5-Methoxy-6-substituted-3-sulfonyl-δ-enlactams from 5-Methoxy-3-sulfonyl Glutarimide:  Synthesis of cis-2-Substituted-3-piperidinols

  摘要：

  [GRAPHICS]A convenient method for the preparation of 5-methoxy-6-substituted-3-sulfonyl-delta-enlactams via regioselective nucleophilic addition to 5-methoxy-3-sulfonyl glutarimide is described. Formal syntheses of L-733,060, CP-99,994, and cassine are also reported.

  DOI：

  10.1021/jo048073e
• 作为产物：
  描述：

  methyl tosyl-L-prolinate 在 二异丁基氢化铝 、 potassium carbonate 、 magnesium 、 三乙胺 、 三氟乙酸酐 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 二氯甲烷 、 环己烷 、 乙腈 为溶剂， 反应 57.5h， 生成 (2S,3s)-1-n-苄基-3-羟基-2-苯基哌啶
  参考文献：
  名称：

  Highly Stereoselective Syntheses of Proline-Derived Vicinal Amino Alcohols through Grignard Addition onto N-Tosylprolinal

  摘要：

  A highly diastereoselective Grignard addition to N-tosyl-l-prolinal has been developed to deliver a variety of proline-derived vicinal amino alcohols in good to excellent yields with high diastereoselectivities. A similar selectivity was also obtained by using N-tosyl-d-prolinal. The methodology has been applied to the synthesis of medicinally important 3-hydroxy-2-phenylpiperidines.

  DOI：

  10.1055/s-0035-1560802

文献信息

• Concise, stereodivergent and highly stereoselective synthesis of <i>cis-</i> and <i>trans</i>-2-substituted 3-hydroxypiperidines – development of a phosphite-driven cyclodehydration
  作者：Peter H Huy、Julia C Westphal、Ari M P Koskinen

  DOI：10.3762/bjoc.10.35

  日期：——

  A concise (5 to 6 steps), stereodivergent, highly diastereoselective (dr up to >19:1 for both stereoisomers) and scalable synthesis (up to 14 g) of cis- and trans-2-substituted 3-piperidinols, a core motif in numerous bioactive compounds, is presented. This sequence allowed an efficient synthesis of the NK-1 inhibitor L-733,060 in 8 steps. Additionally, a cyclodehydration-realizing simple triethylphosphite

  一个简洁（5 到 6 个步骤）、立体发散、高度非对映选择性（两种立体异构体的 dr 高达 >19:1）和可扩展的合成（高达 14 g）顺式和反式 2-取代 3-哌啶醇，一个核心基序在众多生物活性化合物中，介绍了。该序列允许分 8 个步骤有效合成 NK-1 抑制剂 L-733,060。此外，还开发了一种可实现环脱水的简单亚磷酸三乙酯，作为三苯基膦的替代品。在这里，化学计量氧化的 P(V)-副产物（磷酸三乙酯）在后处理过程中很容易通过皂化去除，克服了通常与氧化三苯膦相关的分离困难。
• Stereoselective synthesis of (2S,3S)-3-hydroxy-2-phenylpiperidines, precursors of non-peptidic substance P antagonists
  作者：Olivier Calvez、Nicole Langlois

  DOI：10.1016/s0040-4039(99)01462-8

  日期：1999.9

  (2S)-N-Boc-3-oxo-2-phenylpiperidine 5 and (2S,3S)-N-Boc-3-hydroxy-2-phenylpiperidine 6, known chiral building blocks for the synthesis of non-peptidic substance P antagonists, were prepared from erythro (2S)-N-benzyl 2-hydroxybenzylpyrrolidine derived from (S)-N-methoxy-N-methylpyroglutamide. (C) 1999 Elsevier Science Ltd. All rights reserved.

  (S)-N-Boc-3-酮-2-苯基哌啶（5）和(S,S)-N-Boc-3-羟基-2-苯基哌啶（6），这两种已知的手性构建单元，用于合成非肽类物质P拮抗剂，是从由(S)-N-甲氧基-N-甲基吡咯烷四肽衍生而来的赤藓糖醇-(2S)-N-苄基-2-羟基苯甲酰基吡咯啶制备得到的。©1999 Elsevier Science Ltd. 保留所有权利。
• Catalytic Asymmetric Synthesis of Piperidines from Pyrrolidine: Concise Synthesis of L-733,060
  作者：Julia L. Bilke、Stephen P. Moore、Peter O’Brien、John Gilday

  DOI：10.1021/ol900366m

  日期：2009.5.7

  Catalytic asymmetric deprotonation-aldehyde trapping-ring expansion from a 5- to a 6-ring delivers a concise route to each stereoisomer of β-hydroxy piperidines starting from N-Boc pyrrolidine. The methodology is utilized in a 5-step catalytic asymmetric synthesis of the neorokinin-1 receptor antagonist, (+)-L-733,060.

  从N -Boc吡咯烷开始，催化的不对称去质子醛捕获环从5个环扩展为6个环，为向β-羟基哌啶的每个立体异构体提供了一条简洁的途径。该方法用于新激酶1受体拮抗剂（+）-L-733,060的5步催化不对称合成。
• Asymmetric Hydrogenation of 2-Arylated Cycloalkanones through Dynamic Kinetic Resolution
  作者：Ryoji Noyori、Takeshi Ohkuma、Jing Li

  DOI：10.1055/s-2004-829093

  日期：——

  Asymmetric hydrogenation of 2-arylcycloalkanones with trans-RuCl2(binap)(1,2-diamine) and t-C4H9OK in 2-propanol selectively gives the corresponding cis-2-arylcycloalkanols in excellent enantiomeric purity and high yield. Two synthetic intermediates of biologically active compounds have been prepared by this method.

  用反式-RuCl2(binap)(1,2-二胺)和 t-C4H9OK 在 2-丙醇中对 2-芳基环烷酮进行不对称氢化，可选择性地得到相应的顺式-2-芳基环烷醇，对映体纯度极高，产率也很高。用这种方法制备了两种生物活性化合物的合成中间体。
• Efficient, Stereodivergent Access to 3-Piperidinols by Traceless P(OEt)₃ Cyclodehydration
  作者：Peter H. Huy、Ari M. P. Koskinen

  DOI：10.1021/ol4026588

  日期：2013.10.18

  A stereodivergent and highly diastereoselective (dr up to >19:1 for both isomers), step economic (5-6 steps), and scalable synthesis (up to 14 g) of cis- and trans-2-substituted 3-piperidinols, the core motif of numerous bioactive compounds, providing efficient access to the NK-1 inhibitor L-733,060 is presented. Additionally, a "traceless" (referring to the simplified byproduct separation) cyclodehydration realizing simple P(OEt)(3) as a substitute for PPh3 is developed.