(2R,5S)-N-benzyl-5-[1'-(2'-methoxycarbonyl)ethyl]proline methyl ester | 208037-74-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2R,5S)-N-benzyl-5-[1'-(2'-methoxycarbonyl)ethyl]proline methyl ester
• 英文别名: methyl (2R,5S)-1-benzyl-5-(3-methoxy-3-oxopropyl)pyrrolidine-2-carboxylate
• CAS: 208037-74-5
• 化学式: C₁₇H₂₃NO₄
• 分子量: 305.374
• InChiKey: QJAPEKPNFBFMEI-LSDHHAIUSA-N

物化性质

• 沸点：
  380.5±32.0 °C(Predicted)
• 密度：
  1.132±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2R,5S)-N-benzyl-5-[1'-(2'-methoxycarbonyl)ethyl]proline methyl ester 在 palladium on activated charcoal 4-二甲氨基吡啶 、 sodium hydroxide 、 氢气 、 双氧水 、 双(三甲基硅烷基)氨基钾 、 sodium hydride 、 sodium cyanoborohydride 、 sodium carbonate 、 三氟乙酸 、 sodium iodide 、 sodium nitrite 作用下， 以 四氢呋喃 、 吡啶 、 甲醇 、 乙醇 、 二氯甲烷 、 水 、 乙酸酐 、 溶剂黄146 、 甲苯 、 乙腈 为溶剂， 反应 102.67h， 生成 古卡因
  参考文献：
  名称：

  Enantiospecific Synthesis of Natural (−)-Cocaine and Unnatural (+)-Cocaine from d- and l-Glutamic Acid

  摘要：

  Natural (-)-cocaine and unnatural (+)-cocaine have been synthesized enantiospecifically from D- and L-glutamic acid, respectively. The axial-equatorial substitutents were introduced by a stereo- and regiospecific dipolar cycloaddition to the corresponding (LR,5S)- and (1S,5R)-N-BOC-nortropenes with (ethoxycarbonyl)formonitrile N-oxide. A sequence of subsequent stereochemically controlled transformations converted the fused isoxazoline to the requisite P-hydroxy ester. Synthesis of the key intermediate N-BOC-nortropenes involved construction of the 8-azabicyclo[3.2.1]octane framework by Dieckmann condensation of cis-5-substituted D-and L-proline esters. For comparison, (1R,SS)-N-BOC-nortropene also was derived by degradation from natural cocaine. The cis-5-substituted D-and L-proline esters were obtained by sulfide contraction and subsequent catalytic hydrogenation to induce stereospecifically the C-5 stereochemistry from D-and L-thiopyroglutamate, which in turn were prepared from D-and L-glutamic acids, respectively.

  DOI：

  10.1021/jo980153t
• 作为产物：
  描述：

  3-[(2S,5R)-5-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidin-2-yl]propanoic acid 在 potassium carbonate 、 乙酰氯 作用下， 以 乙腈 为溶剂， 反应 28.0h， 生成 (2R,5S)-N-benzyl-5-[1'-(2'-methoxycarbonyl)ethyl]proline methyl ester
  参考文献：
  名称：

  Enantiospecific Synthesis of Natural (−)-Cocaine and Unnatural (+)-Cocaine from d- and l-Glutamic Acid

  摘要：

  Natural (-)-cocaine and unnatural (+)-cocaine have been synthesized enantiospecifically from D- and L-glutamic acid, respectively. The axial-equatorial substitutents were introduced by a stereo- and regiospecific dipolar cycloaddition to the corresponding (LR,5S)- and (1S,5R)-N-BOC-nortropenes with (ethoxycarbonyl)formonitrile N-oxide. A sequence of subsequent stereochemically controlled transformations converted the fused isoxazoline to the requisite P-hydroxy ester. Synthesis of the key intermediate N-BOC-nortropenes involved construction of the 8-azabicyclo[3.2.1]octane framework by Dieckmann condensation of cis-5-substituted D-and L-proline esters. For comparison, (1R,SS)-N-BOC-nortropene also was derived by degradation from natural cocaine. The cis-5-substituted D-and L-proline esters were obtained by sulfide contraction and subsequent catalytic hydrogenation to induce stereospecifically the C-5 stereochemistry from D-and L-thiopyroglutamate, which in turn were prepared from D-and L-glutamic acids, respectively.

  DOI：

  10.1021/jo980153t

文献信息

• Enantiospecific Synthesis of Natural (−)-Cocaine and Unnatural (+)-Cocaine from <scp>d</scp>- and <scp>l</scp>-Glutamic Acid
  作者：Ronghui Lin、Josep Castells、Henry Rapoport

  DOI：10.1021/jo980153t

  日期：1998.6.1

  Natural (-)-cocaine and unnatural (+)-cocaine have been synthesized enantiospecifically from D- and L-glutamic acid, respectively. The axial-equatorial substitutents were introduced by a stereo- and regiospecific dipolar cycloaddition to the corresponding (LR,5S)- and (1S,5R)-N-BOC-nortropenes with (ethoxycarbonyl)formonitrile N-oxide. A sequence of subsequent stereochemically controlled transformations converted the fused isoxazoline to the requisite P-hydroxy ester. Synthesis of the key intermediate N-BOC-nortropenes involved construction of the 8-azabicyclo[3.2.1]octane framework by Dieckmann condensation of cis-5-substituted D-and L-proline esters. For comparison, (1R,SS)-N-BOC-nortropene also was derived by degradation from natural cocaine. The cis-5-substituted D-and L-proline esters were obtained by sulfide contraction and subsequent catalytic hydrogenation to induce stereospecifically the C-5 stereochemistry from D-and L-thiopyroglutamate, which in turn were prepared from D-and L-glutamic acids, respectively.