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

HRID 1617159노트

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HRID 1617159 반응식
[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]

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

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온도
0 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-ca1c8d5b72584366a8963eff21742650
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08765939B2

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