Cesium fluoride → Methyl 2-fluoro-4-phenylbenzoate

HRID 915637노트

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HRID 915637 반응식
[F:1][C:2]1[CH:11]=[C:10](Br)[CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[C:13]1(B(O)O)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[F-].[Cs+]>CN(C)C=O.O.C(OCC)(=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:7][O:6][C:4]([C:3]1[CH:8]=[CH:9][C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:11][C:2]=1[F:1])=[O:5]

참가 물질

8

반응물 3

HCID 25953Cesium fluorideHCID 66827Phenylboronic AcidHCID 113453114-Bromo-2-fluoro-benzoic acid methyl ester

생성물 1

HCID 69129634Methyl 2-fluoro-4-phenylbenzoate

시약·촉매·용매 4

HCID 167845palladium(II) acetate촉매HCID 962Water용매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

반응 조건

온도
80 °C

실험 절차

Combine methyl 2-fluoro-4-bromobenzoate (1.25 g, 5.36 mmol), phenylboronic acid (1.30 g, 10.72 mmol) and CsF (2.02 g, 13.40 mmol) in dimethylformamide (25 mL) and water (3.0 mL) with stirring. Place the hetereogeneous reaction mixture open to the air in an oil bath maintained at 80° C. After 5 minutes of heating, add Pd(OAc)2 (120 mg, 0.536 mmol) in one portion and stir until reaction turns black. Cool reaction to room temperature, dilute with ethyl acetate and filter through a short plug of celite with additional ethyl acetate. Wash organics with water, dry over magnesium sulfate, filter and evaporate. Purification by flash column chromatography yields 3-fluorobiphenyl-4-carboxylic acid methyl ester as a solid. Dissolve the purified ester in tetrahydrofuran (0.25M) and add an equal volume of 1M sodium hydroxide. Stir vigorously at room temperature for 15 hours. Upon completion, acidify the reaction with conc. HCl and extract with ethyl acetate. Evaporation of the solvent yields 965 mg (84%) of the title compound. MS (m/e): 214.9 (M−).

후처리

  1. temperatureAfter 5 minutes of heating
  2. temperatureCool
  3. customreaction to room temperature
  4. filtrationfilter through a short plug of celite with additional ethyl acetate
  5. dry with materialWash organics with water, dry over magnesium sulfate
  6. filtrationfilter
  7. customevaporate
  8. customPurification by flash column chromatography

출처 및 근거

ORD 기록
ord-33da91d695014e7cad2357a304921973
출처 데이터셋
uspto-grants-2007_09
특허 번호
US07265246B2

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