Water → Ethyl 2-cyano-4-(2-fluorophenyl)-4-oxobutanoate

HRID 554206노트

반응식

HRID 554206 반응식
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8](=[O:10])[CH3:9].C(=O)([O-])[O-].[K+].[K+].[C:17]([CH2:19][C:20]([O:22][CH2:23][CH3:24])=[O:21])#[N:18].O>C(OCC)(=O)C.CC(C)=O.[Cu](Br)Br>[C:17]([CH:19]([CH2:9][C:8]([C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[F:1])=[O:10])[C:20]([O:22][CH2:23][CH3:24])=[O:21])#[N:18]

참가 물질

8

반응물 4

HCID 962WaterHCID 7764Ethyl cyanoacetateHCID 11430Potassium CarbonateHCID 96744o-Fluoroacetophenone

생성물 1

HCID 66924657Ethyl 2-cyano-4-(2-fluorophenyl)-4-oxobutanoate수율 124%

시약·촉매·용매 3

HCID 24611Copper bromide (CuBr2)촉매HCID 180Acetone용매HCID 8857Ethyl Acetate용매2회

실험 절차

To a solution of 2′-fluoroacetophenone (28.6 g) in ethyl acetate (400 mL), copper (II) bromide (92.6 g) was added, and the mixture was heated under reflux for 4 hr. The reaction mixture was cooled to room temperature and the insoluble material was filtered off. The filtrate was concentrated under reduced pressure to give crude 1-bromo-1-(2-fluorophenyl)ethanone (yield 90.5 g) as an oil. Potassium carbonate (88 g) was added to ethyl cyanoacetate (168 g), and the mixture was stirred at 45° C. for 1 hr. A solution (360 mL) of crude 1-bromo-1-(2-fluorophenyl)ethanone (90.5 g) in acetone was added dropwise over 20 min. After completion of the dropwise addition, the mixture was stirred at the same temperature for 1 hr. To the reaction mixture water (300 mL) and ethyl acetate (300 mL) were added, and the mixture was extracted with ethyl acetate. The extract was washed with 10% aqueous sodium dihydrogenphosphate solution and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. An excess ethyl cyanoacetate contained in the obtained oil was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=20:1→4:1) to give the title compound as an oil (yield 64.0 g, about 100%).

후처리

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 4 hr
  3. filtrationthe insoluble material was filtered off
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. customto give crude 1-bromo-1-(2-fluorophenyl)ethanone (yield 90.5 g) as an oil
  6. additionAfter completion of the dropwise addition
  7. stirringthe mixture was stirred at the same temperature for 1 hr
  8. extractionthe mixture was extracted with ethyl acetate
  9. washThe extract was washed with 10% aqueous sodium dihydrogenphosphate solution and saturated brine
  10. dry with materialdried over anhydrous sodium sulfate
  11. concentrationconcentrated under reduced pressure
  12. customwas evaporated under reduced pressure
  13. customthe residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=20:1→4:1)

출처 및 근거

ORD 기록
ord-0a8dcfca6bc94d4d8cb7077df4e0840e
출처 데이터셋
uspto-grants-2011_11
특허 번호
US08048909B2

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