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

HRID 2387813노트

반응식

HRID 2387813 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

반응 조건

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 10 to 20% EtOAc in isohexane to give the subtitle compound as a colorless oil 110.10 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 10 to 20% EtOAc in isohexane

출처 및 근거

ORD 기록
ord-6518e68aec3148c9a54e92417e21f6ed
출처 데이터셋
uspto-grants-2012_09
특허 번호
US08268990B2

반응 노트

불러오는 중…