Potassium Carbonate → HCID 18388216, compound

HRID 2296743Notes

Reaction equation

HRID 2296743 reaction equation
Br[C:2]1[C:3](=[O:8])[O:4][CH2:5][CH2:6][CH:7]=1.[F:9][C:10]1[CH:11]=[C:12](B(O)O)[CH:13]=[CH:14][C:15]=1[F:16].C(=O)([O-])[O-].[K+].[K+].[F-].[K+]>O1CCCC1.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:9][C:10]1[CH:11]=[C:12]([C:2]2[C:3](=[O:8])[O:4][CH2:5][CH2:6][CH:7]=2)[CH:13]=[CH:14][C:15]=1[F:16]

Participants

9

Reactant 4

HCID 11430Potassium CarbonateHCID 522689Potassium FluorideHCID 27343373,4-Difluorobenzeneboronic acidHCID 108560293-bromo-5,6-dihydro-2H-pyran-2-one

Product 1

HCID 18388216HCID 18388216, compoundYield 33.6%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 3-bromo-5,6-dihydropyran-2-one (87.4 g, 0.49mol), 3,4-difluorophenylboronic acid (91.4 g, 0.58 mol), potassium carbonate (99.9 g, 0.72 mol), potassium fluoride (85.4 g, 1.47 mol) and tetrakis(triphenylphosphine)palladium (0) (12 g, 0.01 mol) in tetrahydrofuran (600 ml) was thoroughly degassed and then heated at reflux for 48 hours under an atmosphere of nitrogen. The solution was cooled to room temperature and water (1000 ml) and ethyl acetate (1000 ml) were added. The organic phase was washed with saturated brine and dried (MgSO4) and the solvent removed in vacuo. The residue was dissolved in dichloromethane and the solution filtered through a pad of silica gel. The filtrate was evaporated to dryness and the residue recrystallized from diethyl ether to give the title compound 34.6 g. mp 82-85° C. 1H NMR (360 MHz. CDCl3) δ 2.63 (2H, td J 6.2 Hz and 4.5 Hz), 4.49 (2H, t J 6.3 Hz), 7.01 (1H, t J 4.5 Hz), 7.11-7.23 (2H, m), 7.32-7.38 (1H, m).

Workup

  1. temperatureheated
  2. temperatureat reflux for 48 hours under an atmosphere of nitrogen
  3. washThe organic phase was washed with saturated brine
  4. dry with materialdried (MgSO4)
  5. customthe solvent removed in vacuo
  6. dissolutionThe residue was dissolved in dichloromethane
  7. filtrationthe solution filtered through a pad of silica gel
  8. customThe filtrate was evaporated to dryness
  9. customthe residue recrystallized from diethyl ether

Sources & evidence

ORD record
ord-b9dbf88f80b54005bd18c5c9a176acd9
Source dataset
uspto-grants-2002_12
Patent number
US06489343B2

Reaction notes

Loading…