1,4-Dioxane → 4-Fluoro-3-(pyridin-2-yl)phenylboronic acid

HRID 586254Notes

Reaction equation

HRID 586254 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([F:14])=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=2)[CH:7]=1.[B:15]1(B2OCC(C)(C)CO2)[O:20]CC(C)(C)C[O:16]1.C([O-])(=O)C.[K+].O1CCOCC1>CS(C)=O>[F:14][C:5]1[CH:4]=[CH:3][C:2]([B:15]([OH:20])[OH:16])=[CH:7][C:6]=1[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=1

Participants

6

Reactant 4

HCID 312751,4-DioxaneHCID 517044Potassium AcetateHCID 2734316Bis(neopentyl glycolato)diboronHCID 222853292-(5-Bromo-2-fluorophenyl)pyridine

Product 1

HCID 222853284-Fluoro-3-(pyridin-2-yl)phenylboronic acid

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
85 °C

Procedure

To 2-(5-bromo-2-fluorophenyl)pyridine (544 mg, 2.16 mmol) and bis(neopentyl glycolato)diborane (585 mg, 2.60 mmol) under nitrogen was added dry potassium acetate (450 mg, 4.58 mmol), anhydrous 1,4-dioxane (8 ml) and DMSO (1 ml). The mixture was degassed with nitrogen, and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (50 mg, 3 mol %) was added. After stirring at 85° C. under nitrogen for 15 h, the mixture was cooled to room temperature, and sodium hydroxide solution (20 ml of a 1 M solution) was added. The mixture was stirred for 10 min, and was then extracted twice with diethyl ether. The combined ether extractions were washed with water, then the combined aqueous layers were filtered through a glass fibre filter paper. The pH of the filtrate was adjusted to 6 by the addition of 2 N hydrochloric acid, precipitating a white solid. This was collected by filtration, washed with water and dried in vacuo at 60° C., and was found to be 4-fluoro-3-(pyridin-2-yl)phenylboronic acid (455 mg, 97%): 1H NMR (400 MHz, DMSO) δ 7.30 (1H, dd, J 8.2, 11.7 Hz), 7.41 (1H, m), 7.77 (1H, m), 7.90 (2H, m), 8.16 (2H, s), 8.36 (1H, dd, J 1.6, 8.6 Hz), 8.72 (1H, m).

Workup

  1. customThe mixture was degassed with nitrogen, and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (50 mg, 3 mol %)
  2. additionwas added
  3. temperaturethe mixture was cooled to room temperature
  4. additionsodium hydroxide solution (20 ml of a 1 M solution) was added
  5. stirringThe mixture was stirred for 10 min
  6. extractionwas then extracted twice with diethyl ether
  7. extractionThe combined ether extractions
  8. washwere washed with water
  9. filtrationthe combined aqueous layers were filtered through a glass fibre
  10. filtrationfilter paper
  11. additionThe pH of the filtrate was adjusted to 6 by the addition of 2 N hydrochloric acid
  12. customprecipitating a white solid
  13. filtrationThis was collected by filtration
  14. washwashed with water
  15. customdried in vacuo at 60° C.

Sources & evidence

ORD record
ord-af1e126a8d4547918a3a3ed665cdcb97
Source dataset
uspto-grants-2005_08
Patent number
US06936608B2

Reaction notes

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