Hydrochloric Acid → 2-Fluoro-4-phenylbenzoic acid

HRID 2224728Notes

Reaction equation

HRID 2224728 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>C1COCC1>[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 DMF (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 MgSO4, filter and evaporate. Purification by flash column chromatography yields 3-fluorobiphenyl-4-carboxylic acid methyl ester as a solid. Dissolve the purified ester in THF (0.25M) and add an equal volume of 1M NaOH. 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 (ES): m/z 214.9 (M−H).

Workup

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

Sources & evidence

ORD record
ord-1e7424ba273048c39dbee471fd572666
Source dataset
uspto-grants-2008_05
Patent number
US07378447B2

Reaction notes

Loading…