Cesium fluoride → Methyl 2-fluoro-4-phenylbenzoate

HRID 915637ノート

反応式

HRID 915637 の反応式
[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]

参加物

8

反応物 3

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

生成物 1

HCID 69129634Methyl 2-fluoro-4-phenylbenzoate

試薬・触媒・溶媒 4

HCID 167845palladium(II) acetate触媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
80 °C

実験手順

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−).

後処理

  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

出典と根拠

ORDレコード
ord-33da91d695014e7cad2357a304921973
出典データセット
uspto-grants-2007_09
特許番号
US07265246B2

反応ノート

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