Dimethylformamide → 5-(3,4-Difluorophenyl)-2,3-dimethyl-benzoic acid

HRID 1771817Notes

Reaction equation

HRID 1771817 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH3:12])[C:5]([CH3:11])=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8].[F:13][C:14]1[CH:15]=[C:16](B(O)O)[CH:17]=[CH:18][C:19]=1[F:20].C([O-])([O-])=O.[Na+].[Na+].CN(C=O)C>CCO.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[F:13][C:14]1[CH:15]=[C:16]([C:2]2[CH:3]=[C:4]([CH3:12])[C:5]([CH3:11])=[C:6]([CH:10]=2)[C:7]([OH:9])=[O:8])[CH:17]=[CH:18][C:19]=1[F:20]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 27343373,4-Difluorobenzeneboronic acidHCID 668959895-Bromo-2,3-dimethylbenzoic acid

Product 1

HCID 894452845-(3,4-Difluorophenyl)-2,3-dimethyl-benzoic acidYield 70%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent2×

Conditions

Temperature
100 °C

Procedure

To a mixture of 5-bromo-2,3-dimethyl-benzoic acid (500 mg, 2.18 mmol, 1.0 eq), (3,4-difluorophenyl)boronic acid (378.6 mg, 2.40 mmol, 1.1 eq) and Na2CO3 (693 mg, 6.54 mmol, 3.0 eq) in a mixture of EtOH (2.5 mL), DMF (10 mL) and H2O (2.5 mL) was added Pd(PPh3)4 (126 mg, 0.11 mmol, 0.05 eq) under nitrogen. The mixture was stirred at 100° C. overnight. After cooling to room temperature, water was added and the diluted reaction mixture filtered through celite. The aqueous layer was extracted with EtOAc and the organic extract was discarded. The remaining aqueous layer was acidified to pH 2 by addition of 3M HCl. The resulting mixture was extracted with EtOAc and the combined organic extracts were washed with water and brine, dried (Na2SO4), filtered and evaporated in vacuo to give the title compound as a white solid (400 mg, 70%).

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe diluted reaction mixture
  3. filtrationfiltered through celite
  4. extractionThe aqueous layer was extracted with EtOAc
  5. extractionthe organic extract
  6. additionThe remaining aqueous layer was acidified to pH 2 by addition of 3M HCl
  7. extractionThe resulting mixture was extracted with EtOAc
  8. washthe combined organic extracts were washed with water and brine
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. customevaporated in vacuo

Sources & evidence

ORD record
ord-3415f8a2e6b6415c8fabd44d6304c278
Source dataset
uspto-grants-2016_02
Patent number
US09249085B2

Reaction notes

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