trans-[4-(4-fluorophenyl)piperidine]-3-carboxylic acid

• 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: trans-[4-(4-fluorophenyl)piperidine]-3-carboxylic acid
• 英文别名: (3S,4R)-4-(4-fluorophenyl)piperidine-3-carboxylic acid
• 化学式: C₁₂H₁₄FNO₂
• 分子量: 223.247
• InChiKey: QHBUJTQDWMKVMX-WDEREUQCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  烟酸甲酯 在 palladium on activated charcoal 氢氧化钾 、 1,10-菲罗啉 、 水 、 氢气 、 magnesium 、 copper(l) chloride 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 50.0 ℃ 、413.68 kPa 条件下， 反应 89.17h， 生成 trans-[4-(4-fluorophenyl)piperidine]-3-carboxylic acid
  参考文献：
  名称：

  Diastereoselective Synthesis of trans- 4-Arylpiperidine-3-carboxylic Acid Derivatives from 4-Aryl-1,4-dihydropyridine

  摘要：

  DOI：

  10.3987/com-99-8631

文献信息

• Novel process
  申请人：SmithKline Beecham p.l.c.

  公开号：US20020010155A1

  公开（公告）日：2002-01-24

  A process for the preparation of a 4-aryl-3-oxymethyl-piperidine of structure (1) 1 in which R is hydrogen or an alkyl, arylalkyl, allyl, acyl, carbonyloxyalkyl, carbonyloxyaryl, or carbonyloxyalkylaryl group, and Y is a hydrogen atom or an optionally substituted alkyl, arylalkyl, or aryl group, from a carboxy derivative of structure (2) 2 where A is oxygen or sulphar, X is one or more of hydrogen, or a readily reducible group, Z represents either a hydrogen atom or an OY′ group in which Y′ is independently selected from the same groups as Y, and the broken line circle indicates bonding, appropriate to a tetrahydropyridine, dihydropyridine, pyridine, or piperidine ring said process comprising (a) when Y is a hydrogen atom, reducing the compound of structure (2), or (b) when Y is other than a hydrogen atom (i) forming an ether from the alcohol product of step (a), (ii) etherifying the aldehyde compound of structure (2) in which Z is hydrogen, or (iii) reducing the ester compound of structure (2) in which Z is OY′.

  一种制备结构（1）中的4-芳基-3-氧甲基-哌啶的方法，其中R是氢或烷基、芳基烷基、烯丙基、酰基、羰基氧烷基、羰基氧芳基或羰基氧烷基芳基，Y是氢原子或可选择取代的烷基、芳基烷基或芳基，从结构（2）中的羧衍生物进行，其中A是氧或硫，X是一个或多个氢或易还原基团，Z代表氢原子或OY′基团，其中Y′独立选择自Y相同的基团，中断线圆表示键合，适用于四氢吡啶、二氢吡啶、吡啶或哌啶环的过程包括(a)当Y是氢原子时，还原结构（2）的化合物，或(b)当Y不是氢原子时(i)从步骤（a）的醇产物中形成醚，(ii)使结构（2）中Z为氢的醛化合物醚化，或(iii)还原结构（2）中Z为OY′的酯化合物。
• Process for preparing a piperidine derivative
  申请人：Sumika Fine Chemicals Co., Ltd.

  公开号：US20030144519A1

  公开（公告）日：2003-07-31

  A piperidine derivative, which can be used as an intermediate for pharmaceuticals such as paroxetine useful as antidepressants, represented by the general formula (I): 1 wherein R 1 is hydrogen atom, benzyloxycarbonyl group or tert-butoxycarbonyl group; R 2 is hydroxymethyl group, an alkylsulfonyloxymethyl group having an alkyl moiety of 1 to 2 carbon atoms, phenylsulfonyloxymethyl group which may have methyl group at the 4-position, (3,4-methylenedioxyphenyl)oxymethyl group, carboxyl group or —CO 2 R 7 group in which R 7 is an alkyl group having 1 to 5 carbon atoms, and Z is methylene group or carbonyl group, with proviso that, (A) when R 1 is benzyloxycarbonyl group or tert-butoxycarbonyl group, then R 2 is hydroxymethyl group, an alkylsulfonyloxymethyl group having an alkyl moiety of 1 to 2 carbon atoms, phenylsulfonyloxymethyl group which may have methyl group at the 4-position or (3,4-methylenedioxyphenyl)oxymethyl group, and Z is methylene group; or (B) when R 1 is hydrogen atom and Z is carbonyl group, then R 2 is carboxyl group or —CO 2 R 7 group (R 7 is as defined above); or (C) when R 1 is hydrogen atom and Z is methylene group, then R 2 is hydroxymethyl group

  一种哌啶衍生物，可用作如帕罗西汀等抗抑郁药物的中间体，由通式（I）表示：其中R1为氢原子，苄氧羰基基团或叔丁氧羰基基团；R2为羟甲基基团，具有1至2个碳原子的烷基磺酰氧甲基基团，可能在4位具有甲基基团的苯基磺酰氧甲基基团，（3,4-亚甲二氧基苯基）氧甲基基团，羧基或CO2R7基团，其中R7为具有1至5个碳原子的烷基基团，Z为亚甲基或羰基基团，但有附加条件，即（A）当R1为苄氧羰基基团或叔丁氧羰基基团时，R2为羟甲基基团，具有1至2个碳原子的烷基磺酰氧甲基基团，可能在4位具有甲基基团的苯基磺酰氧甲基基团或（3,4-亚甲二氧基苯基）氧甲基基团，而Z为亚甲基；或（B）当R1为氢原子且Z为羰基基团时，R2为羧基或CO2R7基团（其中R7如上所定义）；或（C）当R1为氢原子且Z为亚甲基时，R2为羟甲基基团。
• Piperidine derivative as intermediates for the preparation of paroxetine and process for their preparation
  申请人：SUMIKA FINE CHEMICALS Co., Ltd.

  公开号：EP0812827A1

  公开（公告）日：1997-12-17

  A piperidine derivative, which can be used as an intermediate for pharmaceuticals such as paroxetine useful as antidepressants, represented by the general formula (I): wherein R1 is hydrogen atom, benzyloxycarbonyl group or tert-butoxycarbonyl group; R2 is hydroxymethyl group, an alkylsulfonyloxymethyl group having an alkyl moiety of 1 to 2 carbon atoms, phenylsulfonyloxymethyl group which may have methyl group at the 4-position, (3,4-methylenedioxyphenyl)oxymethyl group, carboxyl group or -CO2R7 group in which R7 is an alkyl group having 1 to 5 carbon atoms, and Z is methylene group or carbonyl group, with proviso that, (A) when R1 is benzyloxycarbonyl group or tert-butoxycarbonyl group, then R2 is hydroxymethyl group, an alkylsulfonyloxymethyl group having an alkyl moiety of 1 to 2 carbon atoms, phenylsulfonyloxymethyl group which may have methyl group at the 4-position or (3,4-methylenedioxyphenyl)oxymethyl group, and Z is methylene group; or (B) when R1 is hydrogen atom and Z is carbonyl group, then R2 is carboxyl group or -CO2R7 group (R7 is as defined above); or (C) when R1 is hydrogen atom and Z is methylene group, then R2 is hydroxymethyl group. Also processes for the production of the intermediates are described.

  一种哌啶衍生物，可用作抗抑郁药帕罗西汀等药物的中间体，由通式(I)表示： 其中 R1 为氢原子、苄氧羰基或叔丁氧羰基；R2 是羟甲基、具有 1 至 2 个碳原子的烷基的烷磺酰氧基甲基、可在 4 位上具有甲基的苯磺酰氧基甲基、（3,4-亚甲基二氧苯基）氧基甲基、羧基或-CO2R7 基（其中 R7 是具有 1 至 5 个碳原子的烷基），Z 是亚甲基或羰基、但 (A) 当 R1 为苄氧羰基或叔丁氧羰基时，则 R2 为羟甲基、具有 1 至 2 个碳原子的烷基的烷基磺酰氧甲基、在 4 位可能具有甲基的苯基磺酰氧甲基或（3,4-亚甲基二氧苯基）氧甲基，且 Z 为亚甲基；或 (B) 当 R1 为氢原子且 Z 为羰基时，则 R2 为羧基或-CO2R7 基团（R7 如上定义）；或 (C) 当 R1 为氢原子且 Z 为亚甲基时，则 R2 为羟甲基。 此外，还介绍了中间体的生产工艺。
• Optical resolution of a piperidine derivative
  申请人：SUMIKA FINE CHEMICALS Co., Ltd.

  公开号：EP1384711A1

  公开（公告）日：2004-01-28

  The present invention relates to a method for preparing (3S,4R)-trans-4-(4-fluorophenyl)-3-hydroxymethylpiperidine represented by the formula (II): The method comprises the step of optically resolving (3SR,4RS)-trans-4-(4-fluorophenyl)-3-hydroxymethylpiperidine with o-chlorotartranilic acid as an optically active organic acid.

  本发明涉及一种制备式(II)代表的(3S,4R)-反式-4-(4-氟苯基)-3-羟甲基哌啶的方法： 该方法包括以下步骤：用邻氯酒石酸作为光学活性有机酸对(3SR,4RS)-反式-4-(4-氟苯基)-3-羟甲基哌啶进行光学解析。
• Process for drying paroxetine hydrochloride
  申请人：SUMIKA FINE CHEMICALS Co., Ltd.

  公开号：EP1384720A1

  公开（公告）日：2004-01-28

  The present invention relates to a method for drying paroxetine hydrochloride containing 8 to 15% by weight of isopropanol. The method comprises the steps of: (1) drying crystals of paroxetine hydrochloride containing 8 to 15% by weight of isopropanol obtained by the precipitation of crystals of paroxetine hydrochloride from an isopropanol solution of paroxetine hydrochloride, under reduced pressure at 70°C, and (2) drying the resulting paroxetine hydrochloride under a reduced pressure at a temperature of from 80° to 110°C to give paroxetine hydrochloride having an isopropanol content of 0.1 to 5% by weight.

  本发明涉及一种干燥盐酸帕罗西汀的方法，其中含有 8%至 15%（按重量计）的异丙醇。该方法包括以下步骤 (1) 在 70°C 的减压条件下，通过从盐酸帕罗西汀的异丙醇溶液中析出盐酸帕罗西汀结晶而得到的含 8 至 15%（重量）异丙醇的盐酸帕罗西汀结晶的干燥，以及 (2) 在 80° 至 110°C 的温度下减压干燥所得的盐酸帕罗西汀，得到异丙醇含量为 0.1%至 5%（按重量计）的盐酸帕罗西汀。