(+/-)-1,3(R^*),4(R^*)-Trimethyl-4-(3-methoxyphenyl)-piperidine | 76181-74-3

• 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: (+/-)-1,3(R^*),4(R^*)-Trimethyl-4-(3-methoxyphenyl)-piperidine
• 英文别名: (3R,4R)-4-(3-methoxyphenyl)-1,3,4-trimethylpiperidine
• CAS: 76181-74-3；132621-46-6；132621-50-2；132697-05-3；132697-07-5
• 化学式: C₁₅H₂₃NO
• 分子量: 233.354
• InChiKey: KFANEUPOIDZDBG-SWLSCSKDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  12.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (+/-)-1,3(R^*),4(R^*)-Trimethyl-4-(3-methoxyphenyl)-piperidine 在 盐酸 、 Proton Sponge 、 氯甲酸乙烯酯 、 氢氟酸 、 氢溴酸 、 碳酸氢钠 、 甲基磺酰氯 、 三乙胺 作用下， 以 溶剂黄146 、 乙腈 为溶剂， 反应 31.5h， 生成 (+)-1-(3(S)-3-hydroxy-3-cyclohexylpropyl)-3(R),4(R)-dimethyl-4-(3-hydroxyphenyl)piperidine
  参考文献：
  名称：

  Synthesis and absolute configuration of LY255582, a potent opioid antagonist

  摘要：

  DOI：

  10.1021/jo00004a056
• 作为产物：
  描述：

  1,2,3,4-Tetrahydro-4-(3-methoxyphenyl)-1,4-dimethylpyridine 在 platinum on activated charcoal 硫酸 、 氢气 作用下， 以 乙醇 为溶剂， 生成 (+/-)-1,3(R^*),4(R^*)-Trimethyl-4-(3-methoxyphenyl)-piperidine
  参考文献：
  名称：

  Structure-activity relationships of trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine antagonists for .mu.- and .kappa.-opioid receptors

  摘要：

  A series of racemic N-substituted trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidines were evaluated for opioid agonist and antagonist activity at mu and kappa receptors. Several highly potent mu and kappa antagonists were discovered; however, no compounds with high selectivity for either the mu or kappa receptor were identified. Importantly, no derivative was found to have significant opioid agonist activity. Two derivatives were resolved, and the activities of the enantiomers were investigated. Only a limited stereochemical effect on opioid receptor selectivities was observed. The structure-activity relationships described establish the existence of an important lipophilic binding site distal to the nitrogen for both mu and kappa receptors and confirm the pure opioid antagonist pharmacophore nature of the trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine structure.

  DOI：

  10.1021/jm00072a001

文献信息

• First Asymmetric Synthesis of <i>trans</i>-3,4-Dimethyl-4-arylpiperidines
  作者：Daniel P. Furkert、Stephen M. Husbands

  DOI：10.1021/ol0713988

  日期：2007.9.1

  The first asymmetric synthesis of the trans-3,4-dimethyl-4-arylpiperidine opioid antagonist scaffold is reported. C-3 stereochemistry was established via CBS reduction and stereoselective anti-SN2' cuprate displacement of the derived allylic phosphonate. The resultant vinyl bromide was then elaborated to the target compound by Suzuki coupling and trans-selective 4-methylation. Extension of this methodology

  报道了反式3，4-二甲基-4-芳基哌啶类阿片拮抗剂支架的首次不对称合成。C-3立体化学是通过CBS还原和衍生的烯丙基膦酸酯的立体选择性抗SN2'铜酸盐置换建立的。然后通过Suzuki偶联和反式4-甲基化将所得的乙烯基溴精制为目标化合物。该方法的扩展应允许对映体选择性地进入高度取代的哌啶环系统。
• MITCH, CHARLES H.;ZIMMERMAN, DENNIS M.;SNODDY, JOHN D.;REEL, JON K.;CANTR+, J. ORG. CHEM., 56,(1991) N, C. 1660-1663
  作者：MITCH, CHARLES H.、ZIMMERMAN, DENNIS M.、SNODDY, JOHN D.、REEL, JON K.、CANTR+

  DOI：——

  日期：——