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

HRID 1617159ノート

反応式

HRID 1617159 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 to 20% EtOAc in isohexane to give the subtitle compound as a colorless oil 11.10 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 to 20% EtOAc in isohexane

出典と根拠

ORDレコード
ord-ca1c8d5b72584366a8963eff21742650
出典データセット
uspto-grants-2014_07
特許番号
US08765939B2

反応ノート

読み込み中…