(3R,4S)-4-(4-氟苯基)-3-哌啶甲醇 | 179463-85-5

• 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: (3R,4S)-4-(4-氟苯基)-3-哌啶甲醇
• 英文名称: (3SR,4RS)-trans-4-(4-fluorophenyl)-3-hydroxymethylpiperidine
• 英文别名: (3R,4S)-(+)-4-(4'-fluorophenyl)-3-hydroxymethylpiperidine；trans-4-(4'-Fluorophenyl)-3-hydroxymethylpiperidine；trans-4-(p-fluorophenyl)-3-piperidinecarbinol；(+/-)-trans-4-(4-fluorophenyl)-3-hydroxymethylpiperidine；trans-(+/-)-4-(4-fluorophenyl)-3-hydroxymethylpiperidine；rel-[(3R,4S)-4-(4-fluorophenyl)piperidin-3-yl]methanol；(trans-4-(4-Fluorophenyl)piperidin-3-yl)methanol；[(3R,4S)-4-(4-fluorophenyl)piperidin-3-yl]methanol
• CAS: 179463-85-5
• 化学式: C₁₂H₁₆FNO
• 分子量: 209.264
• InChiKey: IBOPBHBOBJYXTD-ZYHUDNBSSA-N

物化性质

• 沸点：
  327.2±37.0 °C(Predicted)
• 密度：
  1.104±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  32.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (3R,4S)-4-(4-氟苯基)-3-哌啶甲醇 在 盐酸 、 sodium carbonate 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 4.0h， 生成 (3R,4S)-(+)-4-(4'-fluorophenyl)-3-hydroxymethylpiperidine hydrochloride
  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：

  (3R,4S)-(+)-N-benzyloxycarbonyl-4-(4'-fluorophenyl)-3-hydroxymethylpiperidine 在 palladium on activated charcoal 氢气 、 sodium carbonate 作用下， 以 乙醇 、 二氯甲烷 、 水 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+

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。
• Substituted phenylpiperidines with serotoninergic activity and enhanced therapeutic properties
  申请人：Gant G. Thomas

  公开号：US20070112031A1

  公开（公告）日：2007-05-17

  Chemical syntheses and medical uses of novel inhibitors of the uptake of monoamine neurotransmitters and pharmaceutically acceptable salts and prodrugs thereof, for the treatment and/or management of psychotropic disorders, anxiety disorder, generalized anxiety disorder, depression, post-traumatic stress disorder, obsessive-compulsive disorder, panic disorder, hot flashes, senile dementia, migraine, hepatopulmonary syndrome, chronic pain, nociceptive pain, neuropathic pain, painful diabetic retinopathy, bipolar depression, obstructive sleep apnea, psychiatric disorders, premenstrual dysphoric disorder, social phobia, social anxiety disorder, urinary incontinence, anorexia, bulimia nervosa, obesity, ischemia, head injury, calcium overload in brain cells, drug dependence, and/or premature ejaculation are described.

  化学合成和新型单胺神经递质摄取抑制剂的医药用途，以及其药用盐和前药，用于治疗和/或管理精神疾病、焦虑症、广泛性焦虑症、抑郁症、创伤后应激障碍、强迫症、恐慌症、潮热、老年痴呆症、偏头痛、肝肺综合征、慢性疼痛、伤害性疼痛、神经病性疼痛、疼痛性糖尿病视网膜病变、双相抑郁症、阻塞性睡眠呼吸暂停、精神疾病、经前期失调性障碍、社交恐惧症、社交焦虑症、尿失禁、厌食症、暴食症、肥胖症、缺血、头部损伤、脑细胞钙超载、药物依赖和/或早泄。
• Process for preparing arylpiperidine carbinol intermediates and derivatives
  申请人：——

  公开号：US20010053862A1

  公开（公告）日：2001-12-20

  A process for the synthesis of arylpiperidine carbinol intermediates and derivatives is disclosed. A preferred process embodiment provides the synthesis of intermediate compounds of structural formula (I) and structural formula (II): 1 where X is halo, C 1 -C 10 alkoxy, C 1 -C 10 haloalkyl, or hydroxy; R 2 and R 3 are each C 1 -C 4 alkyl, and R 2 and R 3 are the same. The compound of structural formula (I) is made by condensing a corresponding cinnamonitrile with a corresponding diester malonate. The compound of structural formula (II) in the (±)-trans configuration is obtained by hydrogenating the compound of structural formula (I). The compounds of structural formula (I) and structural formula (II) are useful chemical intermediates for synthesizing 4-arylpiperidine-3-carbinols and their derivatives in (−)-trans configuration.

  本发明揭示了一种合成芳基哌啶羧醇中间体和衍生物的方法。首选的方法实施方式提供了结构式（I）和结构式（II）的中间化合物的合成：其中X是卤素，C1-C10烷氧基，C1-C10卤代烷基或羟基；R2和R3均为C1-C4烷基，并且R2和R3相同。结构式（I）的化合物是通过将相应的肉桂腈与相应的二酯丙二酸酯缩合而制得的。在（±）-反式构型下，通过氢化结构式（I）的化合物可获得结构式（II）的化合物。结构式（I）和结构式（II）的化合物是合成（-）-反式构型的4-芳基哌啶-3-羧醇及其衍生物的有用化学中间体。
• 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
• Process for producing piperidinecarbinols
  申请人：Asahi Glass Company Ltd.

  公开号：US06197960B1

  公开（公告）日：2001-03-06

  A process for producing a piperidinecarbinol represented by the general formula (2), which comprises reducing the trans isomer of a compound represented by the general formula (1): wherein R1 is a hydrogen atom, a lower alkyl group or an aralkyl group, R2 is a hydrogen atom, a lower alkyl group, an aryl group or an aralkyl group, and X is a hydrogen atom, a halogen atom, an alkyl group, an aryl group, an aralkyl group, an alkoxy group, a dialkylamino group, an alkylthio group, an arylthio group or CmF2m+1— wherein m is an integer of from 1 to 20.

  一种制备通式（2）所示的哌啶基甲醇的方法，包括还原通式（1）所示的化合物的反式异构体：其中R1是氢原子、低碳基或芳基烷基，R2是氢原子、低碳基、芳基或芳基烷基，X是氢原子、卤素原子、烷基、芳基、芳基烷基、烷氧基、二烷基氨基基、烷硫基、芳硫基或CmF2m+1—，其中m是1至20的整数。