Dimethylformamide → 3-(3-Fluorophenyl)-5-fluorobenzoic acid

HRID 1771658Notes

Reaction equation

HRID 1771658 reaction equation
[F:1][C:2]1[CH:3]=[C:4](B(O)O)[CH:5]=[CH:6][CH:7]=1.Br[C:12]1[CH:13]=[C:14]([CH:18]=[C:19]([F:21])[CH:20]=1)[C:15]([OH:17])=[O:16].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.C(OCC)(=O)C.O>[F:21][C:19]1[CH:18]=[C:14]([CH:13]=[C:12]([C:6]2[CH:5]=[CH:4][CH:3]=[C:2]([F:1])[CH:7]=2)[CH:20]=1)[C:15]([OH:17])=[O:16]

Participants

9

Reactant 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 27339863-Fluorophenylboronic acidHCID 27733393-Bromo-5-fluorobenzoic acid

Product 1

HCID 463123233-(3-Fluorophenyl)-5-fluorobenzoic acidYield 90%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 3-fluorophenyl boronic acid (0.7 g, 5.0 mmol, 1.0 eq), 3-bromo-5-fluoro-benzoic acid (1 g, 4.6 mmol, 1.1 eq) and Na2CO3 (1.45 g, 13.7 mmol, 3 eq) in a mixture of EtOH (5 mL), DMF (20 mL) and H2O (5 mL) under N2 was added Pd(PPh3)4 (200 mg, 0.17 mmol, 0.05 eq). The mixture was stirred at 100° C. overnight then cooled to room temperature. Water and ethyl acetate were added and the reaction was filtered through Celite and the aqueous layer was extracted with EtOAc. The organic extract was discarded and the aqueous layer was acidified to pH 4-5 by addition of 1M HCl and extracted with EtOAc. 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 (970 mg, 90%).

Workup

  1. temperaturethen cooled to room temperature
  2. filtrationthe reaction was filtered through Celite
  3. extractionthe aqueous layer was extracted with EtOAc
  4. extractionThe organic extract
  5. additionthe aqueous layer was acidified to pH 4-5 by addition of 1M HCl
  6. extractionextracted with EtOAc
  7. washThe combined organic extracts were washed with water and brine
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. customevaporated in vacuo

Sources & evidence

ORD record
ord-d2dae7b28f4a489c976efff54709bf8a
Source dataset
uspto-grants-2016_02
Patent number
US09249085B2

Reaction notes

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