Trifluoro-methanesulfonic acid (R)-2-(3-chloro-phenyl)-1-methyl-2-oxo-ethyl ester | 291275-48-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: Trifluoro-methanesulfonic acid (R)-2-(3-chloro-phenyl)-1-methyl-2-oxo-ethyl ester
• 英文别名: [(2R)-1-(3-chlorophenyl)-1-oxopropan-2-yl] trifluoromethanesulfonate
• CAS: 291275-48-4
• 化学式: C₁₀H₈ClF₃O₄S
• 分子量: 316.685
• InChiKey: JQYVNKPKYKQLNZ-ZCFIWIBFSA-N

物化性质

• 沸点：
  360.4±42.0 °C(Predicted)
• 密度：
  1.507±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  68.8
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-氨基-2-甲基-1-丙醇 、 Trifluoro-methanesulfonic acid (R)-2-(3-chloro-phenyl)-1-methyl-2-oxo-ethyl ester 以 二氯甲烷 、 乙腈 为溶剂， 以1.39 g的产率得到(2S,3S)-2-(3-氯苯基)-3,5,5-三甲基吗啉-2-醇
  参考文献：
  名称：

  Synthesis and Characterization of in Vitro and in Vivo Profiles of Hydroxybupropion Analogues: Aids to Smoking Cessation

  摘要：

  To create potentially superior aids to smoking cessation and/or antidepressants and to elucidate bupropion's possible mechanisms of action(s), 23 analogues based on its active hydroxymetabolite (2S,35)-4a were synthesized and tested for their abilities to inhibit monoamine uptake and nAChR subtype activities in vitro and acute effects of nicotine in vivo. The 3',4'-dichlorophenyl [(+/-)-4n], naphthyl (4r), and 3-chlorophenyl or 3-propyl analogues 4s and 4t, respectively, had higher inhibitory potency and/or absolute selectivity than (2S,3S)-4a for inhibition of DA, NE, or 5HT uptake. The 3'-fluorophenyl, 3'-bromophenyl, and 4-biphenyl analogues 4c, 4d, and 4l, respectively, had higher potency for antagonism of alpha 4 beta 2-nAChR than (2S,3S)-4a. Several analogues also had higher potency than (2S,35)-4a as antagonists of nicotine-mediated antinociception in the tail-flick assay. The results suggest that compounds acting via some combination of DA, NE, or 5HT inhibition and/or antagonism of alpha 4 beta 2-nAChR can potentially be new pharmacotherapeutics for treatment of nicotine dependence.

  DOI：

  10.1021/jm1003232
• 作为产物：
  描述：

  tert-butyldimethyl[1-(3-chlorophenyl)prop-1-enyloxy]silane 在 AD-mix-β 、 lutidine 、 水 作用下， 以 二氯甲烷 、 叔丁醇 为溶剂， 生成 Trifluoro-methanesulfonic acid (R)-2-(3-chloro-phenyl)-1-methyl-2-oxo-ethyl ester
  参考文献：
  名称：

  Rapid access to enantiopure bupropion and its major metabolite by stereospecific nucleophilic substitution on an α-ketotriflate

  摘要：

  A stereospecific method for the synthesis of enantiopure alpha -aminoketone from its corresponding alpha -hydroxy-ketone via the triflate intermediate is discussed. This strategy provides a rapid and efficient route for the preparation of either enantiomer of bupropion and its biologically active hydroxylated metabolite, (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(00)00349-9

文献信息

• [EN] BUPROPION METABOLITES AND METHODS OF THEIR SYNTHESIS AND USE<br/>[FR] METABOLITES DU BUPROPION ET LEURS PROCEDES DE SYNTHESE ET D'UTILISATION
  申请人：SEPRACOR INC

  公开号：WO2001062257A2

  公开（公告）日：2001-08-30

  Methods and compositions are disclosed which utilize metabolites of bupropion for treating disorders ameliorated by inhibition of neuronal monoamine reuptake. Such disorders include, but are not limited to, sexual dysfunction, affective disorders, cerebral function disorders, cigarette smoking, and incontinence. Methods of making optically pure bupropion metabolites are also disclosed.

  本发明公开了利用丁丙腈代谢物治疗神经元单胺再摄取抑制改善的疾病的方法和组合物。这些疾病包括但不限于性功能障碍、情感障碍、脑功能障碍、吸烟和失禁。本发明还公开了制备光学纯丁丙腈代谢物的方法。
• Rapid access to enantiopure bupropion and its major metabolite by stereospecific nucleophilic substitution on an α-ketotriflate
  作者：Qun K Fang、Zhengxu Han、Paul Grover、Donald Kessler、Chris H Senanayake*、Stephen A Wald

  DOI：10.1016/s0957-4166(00)00349-9

  日期：2000.9

  A stereospecific method for the synthesis of enantiopure alpha -aminoketone from its corresponding alpha -hydroxy-ketone via the triflate intermediate is discussed. This strategy provides a rapid and efficient route for the preparation of either enantiomer of bupropion and its biologically active hydroxylated metabolite, (C) 2000 Elsevier Science Ltd. All rights reserved.
• Synthesis and Characterization of in Vitro and in Vivo Profiles of Hydroxybupropion Analogues: Aids to Smoking Cessation
  作者：Ronald J. Lukas、Ana Z. Muresan、M. Imad Damaj、Bruce E. Blough、Xiaodong Huang、Hernán A. Navarro、S. Wayne Mascarella、J. Brek Eaton、Syndia K. Marxer-Miller、F. Ivy Carroll

  DOI：10.1021/jm1003232

  日期：2010.6.24

  To create potentially superior aids to smoking cessation and/or antidepressants and to elucidate bupropion's possible mechanisms of action(s), 23 analogues based on its active hydroxymetabolite (2S,35)-4a were synthesized and tested for their abilities to inhibit monoamine uptake and nAChR subtype activities in vitro and acute effects of nicotine in vivo. The 3',4'-dichlorophenyl [(+/-)-4n], naphthyl (4r), and 3-chlorophenyl or 3-propyl analogues 4s and 4t, respectively, had higher inhibitory potency and/or absolute selectivity than (2S,3S)-4a for inhibition of DA, NE, or 5HT uptake. The 3'-fluorophenyl, 3'-bromophenyl, and 4-biphenyl analogues 4c, 4d, and 4l, respectively, had higher potency for antagonism of alpha 4 beta 2-nAChR than (2S,3S)-4a. Several analogues also had higher potency than (2S,35)-4a as antagonists of nicotine-mediated antinociception in the tail-flick assay. The results suggest that compounds acting via some combination of DA, NE, or 5HT inhibition and/or antagonism of alpha 4 beta 2-nAChR can potentially be new pharmacotherapeutics for treatment of nicotine dependence.