Carbon Dioxide → 6-Bromo-2-fluoro-3-(trifluoromethoxy)benzoic acid

HRID 1839899Notes

Reaction equation

HRID 1839899 reaction equation
[Br:1][C:2]1[CH:10]=[CH:9][C:8](C(F)(F)F)=[C:7]([F:15])[C:3]=1[C:4]([OH:6])=[O:5].BrC1C=CC([O:23][C:24]([F:27])([F:26])[F:25])=C(F)C=1.C(NC(C)C)(C)C.C([Li])CCC.C(=O)=O>O1CCCC1.O>[Br:1][C:2]1[CH:10]=[CH:9][C:8]([O:23][C:24]([F:27])([F:26])[F:25])=[C:7]([F:15])[C:3]=1[C:4]([OH:6])=[O:5]

Participants

8

Reactant 5

HCID 280Carbon DioxideHCID 7912DiisopropylamineHCID 27822174-Bromo-2-fluoro-1-(trifluoromethoxy)benzeneHCID 101716566-Bromo-2-fluoro-3-(trifluoromethyl)benzoic acidHCID 178418339Butyllithium

Product 1

HCID 101717906-Bromo-2-fluoro-3-(trifluoromethoxy)benzoic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

2-Bromo-6-fluoro-5-trifluoromethylbenzoic acid 50 mmol of 4-bromo-2-fluoro-1-trifluoromethoxybenzene [105529-58-6] are added at −75° C. to a solution of 52.5 mmol of diisopropylamine and 52.5 mmol of n-butyllithium (1.6 M solution in n-hexane) in 100 ml of dry tetrahydrofuran. The reaction mixture is left at this temperature for 2 h and then added to dry ice. Hydrolysis is effected using water, acidification with hydrochloric acid and extraction with tert-butyl methylether. The combined organic extracts are washed with saturated sodium chloride solution and dried over sodium sulfate. After removing the solvent under reduced pressure, the crude product is purified by recrystallization from n-heptane. 2-Bromo-6-fluoro-5-trifluoromethoxybenzoic acid is obtained in the form of colorless crystals. Melting point: 112° C. 1H NMR (300 MHz, DMSO-d6/TMS): δ=7.67 and 7.71 (overlapping multiplets, 2H)—19F NMR (282.4 MHz, 1H broadband decoupled, DMSO-d6/CFCl3): δ=−57.6 (d, 5J(FF)=5 Hz, OCF3), 129.0 (q, 5J(FF)=5 Hz, CF).

Workup

  1. customHydrolysis
  2. extractionwith hydrochloric acid and extraction with tert-butyl methylether
  3. washThe combined organic extracts are washed with saturated sodium chloride solution
  4. dry with materialdried over sodium sulfate
  5. customAfter removing the solvent under reduced pressure
  6. customthe crude product is purified by recrystallization from n-heptane

Sources & evidence

ORD record
ord-d66320f351f14a6ca5385e65470216e3
Source dataset
uspto-grants-2004_01
Patent number
US06677479B2

Reaction notes

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