Potassium Carbonate → HCID 22050302, compound

HRID 1831939Notes

Reaction equation

HRID 1831939 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:14]=[CH:15][CH:16]=1)[CH2:5][N:6]1[CH:11]=[CH:10][C:9]([OH:12])=[CH:8][C:7]1=[O:13].C([O-])([O-])=O.[K+].[K+].[F:23][C:24]1[CH:31]=[C:30]([F:32])[CH:29]=[CH:28][C:25]=1[CH2:26]Br>CC(C)=O>[F:23][C:24]1[CH:31]=[C:30]([F:32])[CH:29]=[CH:28][C:25]=1[CH2:26][O:12][C:9]1[CH:10]=[CH:11][N:6]([CH2:5][C:4]2[CH:14]=[CH:15][CH:16]=[C:2]([F:1])[CH:3]=2)[C:7](=[O:13])[CH:8]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 902971-(Bromomethyl)-2,4-difluorobenzeneHCID 54724162HCID 54724162, compound

Product 1

HCID 22050302HCID 22050302, compoundYield 84%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

To a solution of 1-(3-fluorobenzyl)-4-hydroxy-1H-pyridin-2-one (from Step 2 EXAMPLE 107) (0.92 g, 4.2 mmol) and K2CO3 (1.2 g, 8.4 mmol) in acetone (62 mL) was added 2,4-difluorobenzyl bromide (1.3 g, 6.3 mmol), and the reaction mixture was heated at reflux for 3 h. The reaction mixture was cooled room temperature, concentrated under reduced pressure, and the residue was partitioned between water and EtOAc. The organic solution was washed with brine, dried (Na2SO4), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, eluent methylene chloride to 95:5 methylene chloride/methanol) to provide 4-(2,4-difluorobenzyloxy)-1-(3-fluorobenzyl)-1H-pyridin-2-one as a white solid (1.21 g, 84%): 1H NMR (300 MHz, CDCl3) δ 7.45-7.20 (m, 2H), 7.14 (d, J=8 Hz, 1H), 7.05-6.75 (m, 5H), 6.05 (d, J=3 Hz, 1H), 5.95 (dd, J=5, 3 Hz, 1H), 5.08 (s, 2H), 5.00 (s, 2H).

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureat reflux for 3 h
  3. concentrationconcentrated under reduced pressure
  4. customthe residue was partitioned between water and EtOAc
  5. washThe organic solution was washed with brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customPurification by flash column chromatography (silica, eluent methylene chloride to 95:5 methylene chloride/methanol)

Sources & evidence

ORD record
ord-98269825a2c745fbaab9c82fa6953327
Source dataset
uspto-grants-2006_06
Patent number
US07067540B2

Reaction notes

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