((3S,4R)-4-(3-异丙氧基苯基)-1,3-二甲基哌啶-4-基)碳酸酯 | 143957-08-8

• 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: ((3S,4R)-4-(3-异丙氧基苯基)-1,3-二甲基哌啶-4-基)碳酸酯
• 英文名称: carbonic acid, ethyl (3S,4R)-1,3-dimethyl-4-<3-(1-methylethoxy)phenyl>-4-piperidinyl ester
• 英文别名: cis-(+/-)carbonic acid ethyl 1,3-dimethyl-4-[3-(l-methylethoxy)phenyl]-4-piperidinyl ester；ethyl (3S,4R)-1,3-dimethyl-4-[3-(1-methylethoxy)phenyl]-4-piperidinyl ester carbonic acid；Carbonic acid, (3S,4R)-1,3-diMethyl-4-[3-(1-Methylethoxy)phenyl]-4-piperidinyl ethyl ester (9CI)；[(3S,4R)-1,3-dimethyl-4-(3-propan-2-yloxyphenyl)piperidin-4-yl] ethyl carbonate
• CAS: 143957-08-8
• 化学式: C₁₉H₂₉NO₄
• 分子量: 335.444
• InChiKey: OJGKBIRRFPYKKZ-HNAYVOBHSA-N

物化性质

• 沸点：
  445.8±45.0 °C(Predicted)
• 密度：
  1.09±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  48
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  D-(+)-二对甲基苯甲酰酒石酸 、 ((3S,4R)-4-(3-异丙氧基苯基)-1,3-二甲基哌啶-4-基)碳酸酯 以 乙醇 为溶剂， 反应 17.0h， 生成 ethyl (3S,4R)-1,3-dimethyl-4-[3-(1-methylethoxy)phenyl]-4-piperidinyl ester carbonic acid (+)-D-2,3-bis[(4-methylbenzoyl)oxy]butanedioic acid
  参考文献：
  名称：

  Compositions containing opioid antagonists

  摘要：

  披露了含有阿片受体拮抗剂的组合物，特别是阿尔维莫潘及其在固体剂型中的活性代谢物，其中药物均匀分布，达到所需的生物利用度，并且稳定。还披露了制备和使用含有阿片受体拮抗剂的组合物的方法。通过一系列加工技术和成分选择实现了这些结果。

  公开号：

  US20070092576A1
• 作为产物：
  描述：

  3-溴苯基异丙醚 在 正丁基锂 作用下， 以 乙酸乙酯 为溶剂， 反应 5.5h， 生成 ((3S,4R)-4-(3-异丙氧基苯基)-1,3-二甲基哌啶-4-基)碳酸酯
  参考文献：
  名称：

  Synthesis of trans-3,4-Dimethyl-4-(3-hydroxyphenyl)piperidine Opioid Antagonists:  Application of the Cis-Thermal Elimination of Carbonates to Alkaloid Synthesis

  摘要：

  Improved syntheses of two trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine opioid antagonists from 1,3-dimethyl-4-piperidinone are described. The 1,3 dimethyl-4-arylpiperidinol 23 was selectively dehydrated in a two step process to the 1,3-dimethyl-4-aryl-1,2,3,6-tetrahydropyrodome 26 by the cis-thermal elimination of the corresponding alkyl carbonate derivative at 190 degrees C. In the presence of a basic nitrogen, the success of the elimination was found to be critically dependent upon the nature of the carbonate alkyl group, with Et, i-Bu, and i-Pr being preferred (90% yield). Alkylation of the metalloenamine, formed by deprotonation of 26 with n-BuLi, proceeded regio- and stereospecifically to give the trans-3,4-dimethyl-4-aryl-1,2,3,4-tetrahydrpyridine 27, which was converted in three steps to the common intermediate, (3R,4R)-3,4-dimethyl-4-(3-hydroxyphenyl)-piperidine. LY255582, a centrally-active opioid antagonist, and LY246736-dihydrate, a peripherally-active opioid antagonist, were prepared from 1,3-dimethyl-4-piperidinone in 11.8% yield (8 steps) and 6.2% yield (12 steps), respectively.

  DOI：

  10.1021/jo951403y

文献信息

• Preparation of substituted tetrahydropyridines
  申请人：Eli Lilly and Company

  公开号：US05136040A1

  公开（公告）日：1992-08-04

  A process for preparing certain 1,3,4,4-tetrasubstituted-1,2,3,4-tetrahydropyridines is provided as well as certain 4-carbonate-1,3,4-trisubstituted-piperidines.

  提供了一种制备特定的1,3,4,4-四取代-1,2,3,4-四氢吡啶以及特定的4-碳酸酯-1,3,4-三取代哌啶的方法。
• DEUTERIUM-ENRICHED ALVIMOPAN
  申请人：Czarnik Anthony W.

  公开号：US20090076082A1

  公开（公告）日：2009-03-19

  The present application describes deuterium-enriched alvimopan, pharmaceutically acceptable salt forms thereof, and methods of treating using the same.
• COMPOSITIONS CONTAINING OPIOID ANTAGONISTS
  申请人：Buehler John D.

  公开号：US20120232114A1

  公开（公告）日：2012-09-13

  Compositions containing opioid antagonists, particularly alvimopan and its active metabolite, with improved solubility and bioavailability for oral or parenteral administration, injectable dosage formulations, kits, and methods of making and using same are disclosed. In preferred embodiments, invention provides injectable formulations containing opioid antagonists, particularly alvimopan and its active metabolite, having low solubility that may be readily prepared, are stable during storage, and provide maximum levels of opioid antagonists when administered parenterally, particularly via injection. The results are achieved by a combination of processing techniques and component selection.
• US5136040A
  申请人：——

  公开号：US5136040A

  公开（公告）日：1992-08-04
• US5498718A
  申请人：——

  公开号：US5498718A

  公开（公告）日：1996-03-12