Ethyl Acetoacetate → Methyl 4-(2-(ethoxycarbonyl)-3-oxobutyl)-3-fluorobenzoate

HRID 2387813ノート

反応式

HRID 2387813 の反応式
[H-].[Na+].[C:3]([O:9][CH2:10][CH3:11])(=[O:8])[CH2:4][C:5]([CH3:7])=[O:6].Br[CH2:13][C:14]1[CH:23]=[CH:22][C:17]([C:18]([O:20][CH3:21])=[O:19])=[CH:16][C:15]=1[F:24]>C1COCC1>[CH2:10]([O:9][C:3]([CH:4]([C:5](=[O:6])[CH3:7])[CH2:13][C:14]1[CH:23]=[CH:22][C:17]([C:18]([O:20][CH3:21])=[O:19])=[CH:16][C:15]=1[F:24])=[O:8])[CH3:11]

参加物

5

反応物 3

HCID 8868Ethyl AcetoacetateHCID 24758Sodium hydrideHCID 18766370Methyl 4-(bromomethyl)-3-fluorobenzoate

生成物 1

HCID 68412608Methyl 4-(2-(ethoxycarbonyl)-3-oxobutyl)-3-fluorobenzoate

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
0 °C

実験手順

Sodium hydride (60% dispersion in mineral oil; 2.45 g) was added portionwise over 10 min to a solution of ethyl acetoacetate (7.5 mL) in THF (60 mL) at 0° C. under nitrogen. The resulting mixture was stirred at 0° C. for 10 min and a solution of methyl 4-(bromomethyl)-3-fluorobenzoate (12.1 g) in THF (40 mL) added over 10 min. The mixture was heated to 65° C. for 15 h and allowed to cool. The mixture was poured cautiously into ice/water (300 mL) and the aqueous extracted with EtOAc. The combined organic phase was dried, filtered and evaporated. The crude product was purified by chromatography eluting with 10 to 20% EtOAc in isohexane to give the subtitle compound as a colorless oil 110.10 g.

後処理

  1. temperatureThe mixture was heated to 65° C. for 15 h
  2. temperatureto cool
  3. extractionthe aqueous extracted with EtOAc
  4. customThe combined organic phase was dried
  5. filtrationfiltered
  6. customevaporated
  7. customThe crude product was purified by chromatography
  8. washeluting with 10 to 20% EtOAc in isohexane

出典と根拠

ORDレコード
ord-6518e68aec3148c9a54e92417e21f6ed
出典データセット
uspto-grants-2012_09
特許番号
US08268990B2

反応ノート

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