Hydrochloric Acid → 2-Fluoro-4-phenylbenzoic acid

HRID 915638Notes

Reaction equation

HRID 915638 reaction equation
C[O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[CH:7][C:6]=1[F:17])=[O:4].[OH-].[Na+].Cl>O1CCCC1>[F:17][C:6]1[CH:7]=[C:8]([C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH:9]=[CH:10][C:5]=1[C:3]([OH:4])=[O:2]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 69129634Methyl 2-fluoro-4-phenylbenzoate

Product 1

HCID 113902902-Fluoro-4-phenylbenzoic acidYield 84%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

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−).

Workup

  1. extractionextract with ethyl acetate
  2. customEvaporation of the solvent

Sources & evidence

ORD record
ord-f5705ed4c2b543848ba5f28b583586bb
Source dataset
uspto-grants-2007_09
Patent number
US07265246B2

Reaction notes

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