Hydrochloric Acid → 4-(Difluoromethyl)-2-fluorobenzoic acid

HRID 1772793Notes

Reaction equation

HRID 1772793 reaction equation
[F:1][CH:2]([F:14])[C:3]1[CH:12]=[CH:11][C:6]([C:7]([O:9]C)=[O:8])=[C:5]([F:13])[CH:4]=1.O.[OH-].[Li+].Cl>C1COCC1.O>[F:14][CH:2]([F:1])[C:3]1[CH:12]=[CH:11][C:6]([C:7]([OH:9])=[O:8])=[C:5]([F:13])[CH:4]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 58180909Methyl 4-(difluoromethyl)-2-fluorobenzoate

Product 1

HCID 219534884-(Difluoromethyl)-2-fluorobenzoic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 4-(difluoromethyl)-2-fluorobenzoate (61 mg, 0.27 mmol) in THF (2.7 mL), was added a solution of lithium hydroxide, monohydrate (170 mg, 4.0 mmol) in water (0.90 mL). The mixture was stirred for 3.5 hours. Hydrochloric acid (1 N) was added to adjust the pH to 2, and the product was extracted with ethyl acetate. The extracts were washed twice with water, once with brine, dried over sodium sulfate and concentrated to afford crude acid, used directly in the next step (51 mg, 99%). 1H NMR (300 MHz, d6-dmso): δ 13.56 (br s, 1H), 8.00 (t, 1H), 7.53 (t, 2H), 7.11 (t, 1H).

Workup

  1. extractionthe product was extracted with ethyl acetate
  2. washThe extracts were washed twice with water, once with brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. customto afford crude acid

Sources & evidence

ORD record
ord-116ea6595e0048edb97887644ae2a603
Source dataset
uspto-grants-2016_02
Patent number
US09249145B2

Reaction notes

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