Carbon Dioxide → 2-Fluorobiphenyl-4-carboxylic Acid

HRID 1991444Notes

Reaction equation

HRID 1991444 reaction equation
[Mg].II.Br[C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[C:7]([F:17])[CH:6]=1.[C:18](=[O:20])=[O:19]>C1COCC1>[F:17][C:7]1[CH:6]=[C:5]([CH:10]=[CH:9][C:8]=1[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C:18]([OH:20])=[O:19]

Participants

6

Reactant 4

HCID 280Carbon DioxideHCID 807IodineHCID 5210634-Bromo-2-fluoro-1,1'-biphenyl2×HCID 5462224Magnesium2×

Product 1

HCID 162174932-Fluorobiphenyl-4-carboxylic AcidYield 740.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-10 °C

Procedure

A suspension of magnesium (0.968 g, 3.98 mmol) and a few crystals of iodine in anhyd THF (200 mL) were treated with dropwise addition of 10 mL of a solution of 4-bromo-2-fluorobiphenyl (10.0 g, 3.98 mmol) in THF (100 mL). The mixture was heated to gentle reflux and a reaction ensued. At that time, the remaining solution of 4-bromo-2-fluorobiphenyl was added dropwise to the flask over a 3-minute period. The contents were then stirred at reflux under argon until no magnesium consumption was observed. The reaction mixture was subsequently cooled to −10° C. and treated with dry ice (˜70 g). The reaction mixture was quenched with 20% aqueous hydrochloric acid (50 mL), and the layers were separated. The aqueous phase was extracted with ethyl acetate (2×20 mL), and the combined organic layer was washed with brine (30 mL), dried over anhyd sodium sulfate and concentrated to about ⅓ of its original volume. The contents were treated with hexane (200 mL), and the precipitate was filtered and dried under high vacuum to afford 3-fluoro-4-phenylbenzoic acid (6.37 g, 74%) as a white, crystalline solid. 1H-NMR (DMSO-d6): δ7.48 (m, 3H); 7.59 (m, 2H); 7.66 (dd, J=8.1, 8.1 Hz, 1H); 7.76 (dd, J=1.5, 11.6 Hz, 1H); 7.85 (dd, J=1.5, 8.1 Hz, 1H); 13.30 (br s, 1H). Anal. Calcd for C13H9FO2: C, 72.22; H, 4.20; F, 8.79. Found: C, 71.95; H, 4.11; F, 9.07.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto gentle reflux
  3. customa reaction ensued
  4. customThe reaction mixture was quenched with 20% aqueous hydrochloric acid (50 mL)
  5. customthe layers were separated
  6. extractionThe aqueous phase was extracted with ethyl acetate (2×20 mL)
  7. washthe combined organic layer was washed with brine (30 mL)
  8. dry with materialdried over anhyd sodium sulfate
  9. concentrationconcentrated to about ⅓ of its original volume
  10. additionThe contents were treated with hexane (200 mL)
  11. filtrationthe precipitate was filtered
  12. customdried under high vacuum

Sources & evidence

ORD record
ord-377bd38106964a1d8cc10065bcbaf198
Source dataset
uspto-grants-2010_01
Patent number
US07645878B2

Reaction notes

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