methyl 3,4-trans-N-methyl-4-phenylpiperidine-3-carboxylate | 32221-42-4

• 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: methyl 3,4-trans-N-methyl-4-phenylpiperidine-3-carboxylate
• 英文别名: (+/-)-1-methyl-4t-phenyl-piperidine-3r-carboxylic acid methyl ester；(+/-)-1-Methyl-4t-phenyl-piperidin-3r-carbonsaeure-methylester；methyl (3R,4S)-1-methyl-4-phenylpiperidine-3-carboxylate
• CAS: 32221-42-4；53757-32-7；53757-33-8；53757-41-8
• 化学式: C₁₄H₁₉NO₂
• 分子量: 233.31
• InChiKey: WMVXAQQBRYETCJ-OLZOCXBDSA-N

物化性质

• 沸点：
  316.6±42.0 °C(Predicted)
• 密度：
  1.063±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 3,4-trans-N-methyl-4-phenylpiperidine-3-carboxylate 在 盐酸 作用下， 生成 1-methyl-4-phenylpiperidine-3-carboxylic acid,hydrochloride
  参考文献：
  名称：

  Pyridindene Derivatives. III. Synthesis from Arecoline

  摘要：

  DOI：

  10.1021/jo01354a009
• 作为产物：
  描述：

  phenylmagnesium bromide 、 槟榔碱 以 乙醚 为溶剂， 反应 1.5h， 以20%的产率得到(-)-Methyl 1-Methyl-4β-phenylpiperidine-3β-carboxylate
  参考文献：
  名称：

  Synthesis, inhibition and binding of simple non-nitrogen inhibitors of monoamine transporters

  摘要：

  A series of simple truncated analogues of phenyl tropanes, 2-arylcycloalk-1-enyl carboxylic acid methylesters, were prepared and investigated for their activity towards the dopamine, serotonin and norepinephrine transporters. The compounds were prepared from cyclic ketoesters, which were converted to enolic triflates and reacted with arylboronates using the Suzuki coupling. For comparison the corresponding piperidines were also made and investigated. The new compounds inhibit monoamine-transporters with K-i values ranging from 0.1 to 1000 mu M. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.03.069

文献信息

• [EN] NOVEL PROCESS FOR THE PREPARATION OF 4-ARYL-3-HYDROXYMETHYL-1-METHYLPIPERIDINES.<br/>[FR] NOUVEAU PROCEDE DE PREPARATION DE 4-ARYL-3-HYDROXYMETHYL-1-METHYLPIPERIDINES
  申请人：NATCO PHARMA LTD

  公开号：WO2004043921A1

  公开（公告）日：2004-05-27

  A novel, improved, and general process for the preparation of 4-aryl-3-hydroxymethyl-1-methylpiperidines is disclosed in the present invention. 4-(4-Fluorophenyl)-3-hydroxymethyl-1-methylpiperidine is a well-known intermediate in making the anti-depressant drug, paroxetine ((-)-trans-4-p-fluorophenyl-3-(3',4'-methylenedioxy-phenoxymethyl)piperidine). Novel N-methyl-N-[3-(4-substitutedphenyl (F, Me, OMe))-3-hydroxy]propylamines are prepared from the Mannich salts such as 3-dimethylamino- or 3-(N-methyl-N-benzylamino)-4'-substituted (F, Me, OMe) propiophenone hydrochlorides by conventional methods. The N-methyl-N-[3-(4-substitutedphenyl (H, F, Me, OMe))-3-hydroxy]propylamines thus obtained are reacted with ethyl or methyl acrylate to get the corresponding Michael addition products. The hydroxy group present in the Michael addition products is converted into a facile leaving group and treated with a strong base to get 4-aryl-N-methylpiperidine-3-carboxylates via the intramolecular cyclization in good yields. Reduction of the ester group present in these piperidine-3-carboxylates gave the title compounds as crystalline solids. Present process is easily adaptable for commercial preparation of the paroxetine intermediate (4-(4-fluorophenyl)-3-hydroxymethyl-1-methylpiperidine).

  本发明揭示了一种新颖的、改进的、通用的制备4-芳基-3-羟甲基-1-甲基哌啶的方法。4-(4-氟苯基)-3-羟甲基-1-甲基哌啶是制造抗抑郁药物帕罗西汀((-)-trans-4-p-氟苯基-3-(3',4'-亚甲二氧基苯氧甲基)哌啶)的已知中间体。新型的N-甲基-N-[3-(4-取代苯基(F，Me，OMe))-3-羟基]丙胺可通过常规方法从Mannich盐制备而来，例如3-二甲氨基或3-(N-甲基-N-苄基氨基)-4'-取代(F，Me，OMe)丙酮盐酸盐。因此获得的N-甲基-N-[3-(4-取代苯基(H，F，Me，OMe))-3-羟基]丙胺与乙基或甲基丙烯酸酯反应，得到相应的Michael加成产物。Michael加成产物中存在的羟基转化为容易离去的基团，并用强碱处理，通过分子内环化以良好的产率得到4-芳基-N-甲基哌啶-3-羧酸酯。这些哌啶-3-羧酸酯中存在的酯基还原后，得到了晶体固体的目标化合物。目前的方法易于用于商业制备帕罗西汀中间体(4-(4-氟苯基)-3-羟甲基-1-甲基哌啶)。
• Synthesis, inhibition and binding of simple non-nitrogen inhibitors of monoamine transporters
  作者：Mikkel Due Petersen、Søren Valdgård Boye、Erik Holm Nielsen、Jeanette Willumsen、Steffen Sinning、Ove Wiborg、Mikael Bols

  DOI：10.1016/j.bmc.2007.03.069

  日期：2007.6

  A series of simple truncated analogues of phenyl tropanes, 2-arylcycloalk-1-enyl carboxylic acid methylesters, were prepared and investigated for their activity towards the dopamine, serotonin and norepinephrine transporters. The compounds were prepared from cyclic ketoesters, which were converted to enolic triflates and reacted with arylboronates using the Suzuki coupling. For comparison the corresponding piperidines were also made and investigated. The new compounds inhibit monoamine-transporters with K-i values ranging from 0.1 to 1000 mu M. (C) 2007 Elsevier Ltd. All rights reserved.
• Pyridindene Derivatives. III. Synthesis from Arecoline
  作者：JOHN T. PLATI、ARTHUR K. INGBERMAN、WILHELM WENNER

  DOI：10.1021/jo01354a009

  日期：1957.3