3-oxo-tropane-2,4-dicarboxylic acid dimethyl ester | 100371-46-8

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 托烷生物碱
• 英文名称: 3-oxo-tropane-2,4-dicarboxylic acid dimethyl ester
• 英文别名: 3-Oxo-tropan-2,4-dicarbonsaeure-dimethylester；dimethyl 8-methyl-3-oxo-8-azabicyclo[3.2.1]octane-2,4-dicarboxylate
• CAS: 100371-46-8
• 化学式: C₁₂H₁₇NO₅
• 分子量: 255.271
• InChiKey: GFZRMTCBJHINDD-UHFFFAOYSA-N

物化性质

• 沸点：
  353.9±42.0 °C(Predicted)
• 密度：
  1.240±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  72.9
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-oxo-tropane-2,4-dicarboxylic acid dimethyl ester 在 sodium hydroxide 、 L-酒石酸 、 sodium sulfate 作用下， 生成 (R)-2-carbomethoxy-3-tropinone
  参考文献：
  名称：

  Concerning 2-Carbomethoxytropinone^*

  摘要：

  DOI：

  10.1021/jo01362a022
• 作为产物：
  描述：

  柠檬酸 在 甲醇 、 丁二醛 、 硫酸 、 三氧化硫 、 盐酸甲胺 作用下， 生成 3-oxo-tropane-2,4-dicarboxylic acid dimethyl ester
  参考文献：
  名称：

  Concerning 2-Carbomethoxytropinone^*

  摘要：

  DOI：

  10.1021/jo01362a022

文献信息

• Process for producing optically active tropinonemonocarboxylic acid derivative
  申请人：Nihon Medi-Physics Co., Ltd.

  公开号：US06486323B1

  公开（公告）日：2002-11-26

  An optically active tropinonemonocarboxylic acid ester derivative useful as an intermediate for synthesis of optically active tropane derivatives was obtained by reacting succindialdehyde with an organic amine and acetonedicarboxylic acid ester to obtain a tropinonedicarboxylic acid ester derivative, and then subjecting this derivative to enzyme-catalyzed asymmetric dealkoxy-carbonylation. Since anhydroecgonine methyl ester derived from the optically active tropinone-monocarboxylic acid ester derivative by reduction and dehydration had the same direction of optical rotation as in the case of anhydroecgonine methyl ester obtained from natural cocaine, it was proved that the obtained optically active tropinonemonocarboxylic acid ester derivative had the same absolute configuration as that of natural cocaine. The yield of the optically active tropinonemonocarboxylic acid ester derivative from the asymmetric dealkoxycarbonylation was 30 to 50 mol %, and its optical purity was 70 to 97% ee. In addition, it was found that a crystalline optically active anhydroecgonine carboxylic acid ester derivative can be obtained by reducing and then dehydrating the optically active tropinonemonocarboxylic acid ester derivative and that its optical purity can easily be increased by recrystallization.

  通过将琥珀醛与有机胺和乙二酸二甲酯反应，得到了一种具有光学活性的环戊酮单羧酸酯衍生物，可用作合成具有光学活性的托帕甲基衍生物的中间体。然后将这种衍生物经过酶催化的不对称去烷氧羰基化，得到了一种环戊酮二羧酸酯衍生物。由于通过还原和脱水得到的光学活性环戊酮单羧酸酯衍生物衍生的无水异恶康宁甲酯的旋光方向与从天然可卡因中获得的无水异恶康宁甲酯相同，证明所得的光学活性环戊酮单羧酸酯衍生物具有与天然可卡因相同的绝对构型。从不对称去烷氧羰基化中得到的光学活性环戊酮单羧酸酯衍生物的产率为30至50摩尔％，其光学纯度为70至97％ee。此外，发现可以通过还原然后脱水光学活性环戊酮单羧酸酯衍生物，得到结晶的光学活性无水异恶康宁羧酸酯衍生物，并且通过再结晶可以轻松提高其光学纯度。
• Process for producing optically active tropinonemonocarboxylic acid ester derivative
  申请人：NIHON MEDI-PHYSICS CO., LTD.

  公开号：US20030065183A1

  公开（公告）日：2003-04-03

  An optically active tropinonemonocarboxylic acid ester derivative useful as an intermediate for synthesis of optically active tropane derivatives was obtained by reacting succindialdehyde with an organic amine and acetonedicarboxylic acid ester to obtain a tropinonedicarboxylic acid ester derivative, and then subjecting this derivative to enzyme-catalyzed asymmetric dealkoxy-carbonylation. Since anhydroecgonine methyl ester derived from the optically active tropinone-monocarboxylic acid ester derivative by reduction and dehydration had the same direction of optical rotation as in the case of anhydroecgonine methyl ester obtained from natural cocaine, it was proved that the obtained optically active tropinonemonocarboxylic acid ester derivative had the same absolute configuration as that of natural cocaine. The yield of the optically active tropinonemonocarboxylic acid ester derivative from the asymmetric dealkoxycarbonylation was 30 to 50 mol %, and its optical purity was 70 to 97% ee. In addition, it was found that a crystalline optically active anhydroecgonine carboxylic acid ester derivative can be obtained by reducing and then dehydrating the optically active tropinonemonocarboxylic acid ester derivative and that its optical purity can easily be increased by recrystallization.

  通过将琥珀二醛与有机胺和乙酰二羧酸酯反应得到了一种光学活性的茎叶酮单羧酸酯衍生物，可用作合成光学活性茎曲烷衍生物的中间体。然后将这种衍生物经过酶催化的不对称脱醚羰基化反应。通过还原和脱水，从光学活性的茎叶酮单羧酸酯衍生物得到的无水异甘氨酸甲酯旋光方向与从天然可卡因中获得的无水异甘氨酸甲酯相同，证明获得的光学活性茎叶酮单羧酸酯衍生物具有与天然可卡因相同的绝对构型。从不对称脱醚羰基化反应中得到的光学活性茎叶酮单羧酸酯衍生物的产率为30至50摩尔％，其光学纯度为70至97％ ee。此外，还发现通过还原然后脱水，可以获得结晶的光学活性无水异甘氨酸羧酸酯衍生物，并且可以通过重结晶轻松提高其光学纯度。
• PROCESS FOR PRODUCING OPTICALLY ACTIVE TROPINONE MONOCARBOXYLIC ACID DERIVATIVE
  申请人：Nihon Medi-Physics Co., Ltd.

  公开号：EP1118674A1

  公开（公告）日：2001-07-25

  An optically active tropinonemonocarboxylic acid ester derivative useful as an intermediate for synthesis of optically active tropane derivatives was obtained by reacting succindialdehyde with an organic amine and acetonedicarboxylic acid ester to obtain a tropinonedicarboxylic acid ester derivative, and then subjecting this derivative to enzyme-catalyzed asymmetric dealkoxy-carbonylation. Since anhydroecgonine methyl ester derived from the optically active tropinone-monocarboxylic acid ester derivative by reduction and dehydration had the same direction of optical rotation as in the case of anhydroecgonine methyl ester obtained from natural cocaine, it was proved that the obtained optically active tropinonemonocarboxylic acid ester derivative had the same absolute configuration as that of natural cocaine. The yield of the optically active tropinonemonocarboxylic acid ester derivative from the asymmetric dealkoxycarbonylation was 30 to 50 mol%, and its optical purity was 70 to 97%ee. In addition, it was found that a crystalline optically active anhydroecgonine carboxylic acid ester derivative can be obtained by reducing and then dehydrating the optically active tropinonemonocarboxylic acid ester derivative and that its optical purity can easily be increased by recrystallization.

  将琥珀醛与有机胺和丙酮羧酸酯反应，得到一种具有光学活性的托品酮羧酸酯衍生物，然后将这种衍生物进行酶催化的不对称脱烷氧羰基化反应，得到一种具有光学活性的托品酮羧酸酯衍生物，这种衍生物可用作合成具有光学活性的托烷衍生物的中间体。由于通过还原和脱水从具有光学活性的托品酮一羧酸酯衍生物中得到的羟基可可碱甲酯与从天然可卡因中得到的羟基可可碱甲酯具有相同的旋光方向，因此证明所得到的具有光学活性的托品酮一羧酸酯衍生物与天然可卡因具有相同的绝对构型。通过不对称脱烷氧羰基化得到的具有光学活性的托品右旋羧酸酯衍生物的产率为 30 至 50 摩尔%，光学纯度为 70 至 97%ee。此外，研究还发现，通过还原然后脱水，可以得到结晶的光学活性安氢壬酸酯衍生物，而且其光学纯度很容易通过重结晶提高。
• Novel asymmetric dealkoxycarbonylation of 3-oxo-8-azabicyclo[3.2.1]-octane-2,4-dicar☐ylates using porcine liver esterase: A new route to (−)-anhydroecgonine methyl ester
  作者：Manabu Node、Soichi Nakamura、Daisaku Nakamura、Takahiro Katoh、Kiyoharu Nishide

  DOI：10.1016/s0040-4039(99)00976-4

  日期：1999.7

  The porcine liver esterase-catalyzed dealkoxycarbonylation of 8-benzyl-3-oxo-8-azabicyclo[3.2.1]octane-2,4-dicarboxylates (4) was found to give high enantiomeric excess of the desymmetrized keto ester (5). This novel dealkoxylcarbonylation opened a new route to the asymmetric synthesis of (1R)cocaine related radiopharmaceuticals such as (1R)-beta-CIT, for diagnosis of Parkinson's disease. (C) 1999 Elsevier Science Ltd. All rights reserved.
• Mannich; Veit, Chemische Berichte, 1935, vol. 68, p. 506,509
  作者：Mannich、Veit

  DOI：——

  日期：——