2-[2-(difluoromethoxy)benzylidene]methyl acetoacetate | 400884-01-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: 2-[2-(difluoromethoxy)benzylidene]methyl acetoacetate
• 英文别名: methyl (2Z)-2-[[2-(difluoromethoxy)phenyl]methylidene]-3-oxobutanoate
• CAS: 400884-01-7
• 化学式: C₁₃H₁₂F₂O₄
• 分子量: 270.233
• InChiKey: NNSMPSAXRQWUOR-YFHOEESVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-[2-(difluoromethoxy)benzylidene]methyl acetoacetate 在 氢氧化钾 作用下， 以 乙醇 为溶剂， 反应 12.0h， 生成 4-[2-(difluoromethoxy)phenyl]-5-(methoxycarbonyl)-2,6-dimethyl-1,4-dihydro-3-pyridinecarboxylic acid
  参考文献：
  名称：

  Effect of Acyl Chain Length and Branching on the Enantioselectivity of Candida rugosa Lipase in the Kinetic Resolution of 4-(2-Difluoromethoxyphenyl)-Substituted 1,4-Dihydropyridine 3,5-Diesters

  摘要：

  Since 2,6-dimethyl-4-aryl-1,4-dihydropyridine 3,5-diesters themselves are not hydrolyzed by commercially available hydrolases, derivatives with spacers containing a hydrolyzable group were prepared. Seven acyloxymethyl esters of 5-methyl- and 5-(2-propoxyethyl) 4-[2-(difluoromethoxy)phenyl]-2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylate were synthesized and subjected to Candida rugosa lipase (CRL) catalyzed hydrolysis in wet diisopropyl ether. A methyl ester at the 5-position and a long or branched acyl chain at C3 gave the highest enantiomeric ratio (E values). The most stereoselective reaction (E = 21) was obtained with 3-[(isobutyryloxy)methyl] 5-methyl 4-(2-difluoromethoxyphenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, and this compound was used to prepare both enantiomers of 3-methyl 5-(2-propoxyethyl) 4-[2-(difluoromethoxy)phenyl]2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylate. The absolute configuration of the enzymatically produced carboxylic acid was established to be 4R by X-ray crystallographic analysis of its 1-(R)-phenylethyl amide.

  DOI：

  10.1021/jo0104025
• 作为产物：
  描述：

  (二氟甲氧基)苯甲醛 、 乙酰乙酸甲酯 在 哌啶 、 溶剂黄146 作用下， 以 异丙醇 为溶剂， 反应 6.0h， 以53.2%的产率得到2-[2-(difluoromethoxy)benzylidene]methyl acetoacetate
  参考文献：
  名称：

  Effect of Acyl Chain Length and Branching on the Enantioselectivity of Candida rugosa Lipase in the Kinetic Resolution of 4-(2-Difluoromethoxyphenyl)-Substituted 1,4-Dihydropyridine 3,5-Diesters

  摘要：

  Since 2,6-dimethyl-4-aryl-1,4-dihydropyridine 3,5-diesters themselves are not hydrolyzed by commercially available hydrolases, derivatives with spacers containing a hydrolyzable group were prepared. Seven acyloxymethyl esters of 5-methyl- and 5-(2-propoxyethyl) 4-[2-(difluoromethoxy)phenyl]-2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylate were synthesized and subjected to Candida rugosa lipase (CRL) catalyzed hydrolysis in wet diisopropyl ether. A methyl ester at the 5-position and a long or branched acyl chain at C3 gave the highest enantiomeric ratio (E values). The most stereoselective reaction (E = 21) was obtained with 3-[(isobutyryloxy)methyl] 5-methyl 4-(2-difluoromethoxyphenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, and this compound was used to prepare both enantiomers of 3-methyl 5-(2-propoxyethyl) 4-[2-(difluoromethoxy)phenyl]2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylate. The absolute configuration of the enzymatically produced carboxylic acid was established to be 4R by X-ray crystallographic analysis of its 1-(R)-phenylethyl amide.

  DOI：

  10.1021/jo0104025

文献信息

• Effect of Acyl Chain Length and Branching on the Enantioselectivity of <i>Candida </i><i>r</i><i>ugosa</i> Lipase in the Kinetic Resolution of 4-(2-Difluoromethoxyphenyl)-Substituted 1,4-Dihydropyridine 3,5-Diesters
  作者：Arkadij Sobolev、Maurice C. R. Franssen、Brigita Vigante、Brigita Cekavicus、Raivis Zhalubovskis、Huub Kooijman、Anthony L. Spek、Gunars Duburs、Aede de Groot

  DOI：10.1021/jo0104025

  日期：2002.1.1

  Since 2,6-dimethyl-4-aryl-1,4-dihydropyridine 3,5-diesters themselves are not hydrolyzed by commercially available hydrolases, derivatives with spacers containing a hydrolyzable group were prepared. Seven acyloxymethyl esters of 5-methyl- and 5-(2-propoxyethyl) 4-[2-(difluoromethoxy)phenyl]-2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylate were synthesized and subjected to Candida rugosa lipase (CRL) catalyzed hydrolysis in wet diisopropyl ether. A methyl ester at the 5-position and a long or branched acyl chain at C3 gave the highest enantiomeric ratio (E values). The most stereoselective reaction (E = 21) was obtained with 3-[(isobutyryloxy)methyl] 5-methyl 4-(2-difluoromethoxyphenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, and this compound was used to prepare both enantiomers of 3-methyl 5-(2-propoxyethyl) 4-[2-(difluoromethoxy)phenyl]2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylate. The absolute configuration of the enzymatically produced carboxylic acid was established to be 4R by X-ray crystallographic analysis of its 1-(R)-phenylethyl amide.