Potassium Carbonate → 3-bromo-1-(3-bromomethyl-2-fluorobenzyl)-4-(2,4-difluorobenzyloxy)-1H-pyridin-2-one

HRID 1866914

Reaction equation

HRID 1866914 reaction equation
[Br:1][C:2]1[C:3](=[O:18])[NH:4][CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17].C([O-])([O-])=O.[K+].[K+].[Br:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([CH2:33]Br)[C:28]=1[F:35]>CN(C=O)C>[Br:1][C:2]1[C:3](=[O:18])[N:4]([CH2:33][C:29]2[CH:30]=[CH:31][CH:32]=[C:27]([CH2:26][Br:25])[C:28]=2[F:35])[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 27360031,3-Bis(bromomethyl)-2-fluorobenzeneHCID 220508323-bromo-4-(2,4-difluorobenzyloxy)-1H-pyridin-2-one

Product 1

HCID 220504863-bromo-1-(3-bromomethyl-2-fluorobenzyl)-4-(2,4-difluorobenzyloxy)-1H-pyridin-2-oneYield 49%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of 3-bromo-4-(2,4-difluorobenzyloxy)-1H-pyridin-2-one (from Step 3, Example 74) (0.3 g, 0.95 mmol) in DMF (26 mL) was added K2CO3 (0.26 g, 1.9 mmol) and 2,6-bis(bromomethyl)fluorobenzene (1.6 g, 5.7 mmol), and the reaction mixture was stirred at 110° C. for 3 h. The reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. The residue was diluted with a 50% aqueous solution of brine, and the aqueous layer was extracted with EtOAc (3×50 mL). The combined organics were washed with water, dried (Na2SO4), filtered, and the solvent was removed under reduced pressure. Purification by flash column chromatography (silica, eluent 99:1 to 95:5 methylene chloride/methanol) afforded 3-bromo-1-(3-bromomethyl-2-fluorobenzyl)-4-(2,4-difluorobenzyloxy)-1H-pyridin-2-one as an off-white solid (0.24 g, 49%): 1H NMR (300 MHz, CDCl3) δ 7.55-7.40 (m, 3H), 7.35-7.25 (m, 1H), 7.10-7.05 (m, 1H), 7.00-6.80 (m, 2H), 6.14 (d, J=6 Hz, 1H), 5.22 (s, 2H), 5.19 (s, 2H), 4.50 (s, 2H).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customthe solvent was removed under reduced pressure
  3. additionThe residue was diluted with a 50% aqueous solution of brine
  4. extractionthe aqueous layer was extracted with EtOAc (3×50 mL)
  5. washThe combined organics were washed with water
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. customthe solvent was removed under reduced pressure
  9. customPurification by flash column chromatography (silica, eluent 99:1 to 95:5 methylene chloride/methanol)

Sources & evidence

ORD record
ord-b7d7a1f9fc1e46b396012fe182843499
Source dataset
uspto-grants-2009_12
Patent number
US07629363B2

Linked notes

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