(3R,4S)-(+)-4-(4'-fluorophenyl)-3-hydroxymethyl-N-phenyloxycarbonylpiperidine | 392328-31-3

• 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: (3R,4S)-(+)-4-(4'-fluorophenyl)-3-hydroxymethyl-N-phenyloxycarbonylpiperidine
• 英文别名: phenyl (3R,4S)-4-(4-fluorophenyl)-3-(hydroxymethyl)piperidine-1-carboxylate
• CAS: 392328-31-3
• 化学式: C₁₉H₂₀FNO₃
• 分子量: 329.371
• InChiKey: ABYCLJOHMWJJKI-CRAIPNDOSA-N

物化性质

• 沸点：
  472.8±45.0 °C(Predicted)
• 密度：
  1.230±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3R,4S)-(+)-4-(4'-fluorophenyl)-3-hydroxymethyl-N-phenyloxycarbonylpiperidine 在 palladium on activated charcoal 氢氧化钾 、 氢气 、 sodium carbonate 作用下， 以 乙醇 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 51.0h， 生成 (3R,4S)-4-(4-氟苯基)-3-哌啶甲醇
  参考文献：
  名称：

  Enzymatic Resolution of trans-4-(4‘-Fluorophenyl)-3-hydroxymethylpiperidines, Key Intermediates in the Synthesis of (−)-Paroxetine

  摘要：

  Two Candida antarctica lipases catalyze the enantioselective acylation of N-substituted trans-4(4'-fluorophenyl)-3-hydroxymethylpiperidines in organic solvents. These two lipases show opposite stereochemical preference in these processes. Both enantiomers can be obtained in their optically pure forms. The (3S,4R) isomer, is an intermediate for the synthesis of (-)-Paroxetine.

  DOI：

  10.1021/jo010809+
• 作为产物：
  描述：

  (+/-)-trans-3-ethoxycarbonyl-4-(4'-fluorophenyl)piperidin-2,6-dione 在 lithium aluminium tetrahydride 、 sodium carbonate 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 13.0h， 生成 (3R,4S)-(+)-4-(4'-fluorophenyl)-3-hydroxymethyl-N-phenyloxycarbonylpiperidine
  参考文献：
  名称：

  Enzymatic Resolution of trans-4-(4‘-Fluorophenyl)-3-hydroxymethylpiperidines, Key Intermediates in the Synthesis of (−)-Paroxetine

  摘要：

  Two Candida antarctica lipases catalyze the enantioselective acylation of N-substituted trans-4(4'-fluorophenyl)-3-hydroxymethylpiperidines in organic solvents. These two lipases show opposite stereochemical preference in these processes. Both enantiomers can be obtained in their optically pure forms. The (3S,4R) isomer, is an intermediate for the synthesis of (-)-Paroxetine.

  DOI：

  10.1021/jo010809+

文献信息

• Optically pure paroxetine precursos
  申请人：Astur-Pharma, S.A.

  公开号：EP1431287A1

  公开（公告）日：2004-06-23

  A biocatalytic process to obtain optically enriched precursors of trans-4-(4-fluorophenyl)-3-hydroxymethylpiperidines,based on the enzymatic resolution of racemic derivatives of general formula III (where R3 is preferably phenyl or benzyl) using cyclic anhydrydes or the Meldrum's acid (2,2-dimethyl-1,3-dioxane-4,6-dione) as acylating agents of the hydroxyl group. Depending on the enzyme and the chosen reaction conditions, either of the two enantiomers may be obtained with high enantiomeric purity. These compounds are important intermediates in the synthesis of the paroxetine anti-depressive agent.

  一种生物催化过程，用于获得光学富集的trans-4-(4-氟苯基)-3-羟甲基哌啶衍生物的前体，基于对具有一般式III（其中R3最好是苯基或苄基）的外消旋衍生物进行酶解析，使用环酐或Meldrum's酸（2,2-二甲基-1,3-二氧杂环己-4,6-二酮）作为羟基的酰化剂。根据酶和选择的反应条件，可以获得高对映纯度的两种对映体中的任一种。这些化合物是帕罗西汀抗抑郁剂合成中的重要中间体。
• Optically pure paroxetine precursors
  申请人：Astur Pharma

  公开号：US20030018048A1

  公开（公告）日：2003-01-23

  A biocatalytic process to obtain optically enriched derivatives of trans-4-(4-fluorophenyl)-3-hydroxymethylpiperidines, based on the enzymatic resolution of racemic precursors of formula III (where R 3 is preferably phenyl or benzyl) by acylation of the hydroxyl group. Depending on the enzyme and the reaction conditions, either of the two enantiomers may be obtained with high enantiomeric purity. These compounds are important intermediates in the synthesis of the paroxetine anti-depressive agent. 1

  一种生物催化过程，用于获取光学纯度富集的trans-4-(4-氟苯基)-3-羟甲基哌啶衍生物，基于通过羟基酰化酶解racemic配体III（其中R3最好是苯基或苄基）获得。根据酶和反应条件，可以获得两个对映体之一，具有高对映纯度。这些化合物是合成帕罗西汀抗抑郁剂的重要中间体。1
• Anhydrides as Acylating Agents in the Enzymatic Resolution of an Intermediate of (−)-Paroxetine
  作者：Gonzalo de Gonzalo、Rosario Brieva、Víctor M. Sánchez、Miguel Bayod、Vicente Gotor

  DOI：10.1021/jo034120b

  日期：2003.4.1

  A new chemoenzymatic method for the preparation of an intermediate of (-)-Paroxetine is reported. Cyclic anhydrides are used as acylating agents in the lipase-catalyzed esterification of trans-4-(4'-fluorophenyl)-3-hydroxymethyl-N-phenyloxycarbonylpiperidine in organic solvents. The best enantioselectivities are obtained with two different lipases from Candida antarctica. These two lipases show opposite

  报道了一种新的化学酶法制备（-）-帕罗西汀中间体的方法。在有机溶剂中，在脂肪酶催化的反式-4-（4'-氟苯基）-3-羟甲基-N-苯氧基羰基哌啶的酯化反应中，环酸酐被用作酰化剂。用来自南极假丝酵母的两种不同的脂肪酶可获得最佳的对映选择性。这两种脂肪酶在这些过程中显示出相反的立体化学偏好，因此两种对映异构体都可以以其光学纯的形式获得。（3S，4R）异构体是合成（-）-帕罗西汀的中间体。
• Enzymatic Resolution of <i>trans</i>-4-(4‘-Fluorophenyl)-3-hydroxymethylpiperidines, Key Intermediates in the Synthesis of (−)-Paroxetine
  作者：Gonzalo de Gonzalo、Rosario Brieva、Víctor M. Sánchez、Miguel Bayod、Vicente Gotor

  DOI：10.1021/jo010809+

  日期：2001.12.1

  Two Candida antarctica lipases catalyze the enantioselective acylation of N-substituted trans-4(4'-fluorophenyl)-3-hydroxymethylpiperidines in organic solvents. These two lipases show opposite stereochemical preference in these processes. Both enantiomers can be obtained in their optically pure forms. The (3S,4R) isomer, is an intermediate for the synthesis of (-)-Paroxetine.