Bromide ion → 3-bromo-4-(4-chlorophenyl)-6-methylpyridin-2(1H)-one

HRID 2101375Notes

Reaction equation

HRID 2101375 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[C:12]([CH3:14])[NH:11][C:10](=[O:15])[CH:9]=2)=[CH:4][CH:3]=1.C1C(=O)N([Br:23])C(=O)C1.[Br-].BrC1C(C2C=CC(Cl)=CC=2)=CC(=O)NC=1C>CO>[Br:23][C:9]1[C:10](=[O:15])[NH:11][C:12]([CH3:14])=[CH:13][C:8]=1[C:5]1[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=1

Participants

6

Reactant 4

HCID 259Bromide ionHCID 67184N-bromobutanimide2×HCID 574686404-(4-chloro-phenyl)-6-methyl-1H-pyridin-2-one2×HCID 577993945-bromo-4-(4-chlorophenyl)-6-methylpyridin-2(1H)-one

Product 1

HCID 577993793-bromo-4-(4-chlorophenyl)-6-methylpyridin-2(1H)-oneYield 58.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
40 °C

Procedure

A suspension of 4-(4-chlorophenyl)-6-methylpyridin-2(1H)-one (0.44 g, 2.0 mmol) in methanol (30 mL) was refluxed until a clear solution formed. The solution was allowed to cool to 40° C., then NBS (285 mg, 1.6 mmol) was added in small portions over 30 min. After completion of the addition, analysis by HPLC/MS indicated about 40% of the starting 4-(4-chlorophenyl)-6-methylpyridin-2(1H)-one remained. Additional NBS (142 mg, 0.8 mmol) was added in portions over 10 min. The reaction mixture was stirred at room temperature for 1 h, then concentrated under reduced pressure. The residue was triturated with a mixture of water (50 mL) and EtOAc (50 mL), and filtered to obtain a solid product which contained mainly the regioisomeric bromide, 5-bromo-4-(4-chlorophenyl)-6-methylpyridin-2(1H)-one. The filtrate was extracted with EtOAc (30 mL×3). The combined extracts were washed with aqueous saturated NaCl solution, dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified using a silica gel cartridge (80 g) eluted with a gradient of EtOAc (30-100%) in hexanes to afford 280 mg (47%) of the title product as a white solid. HPLC/MS: retention time=3.15 min, [M+H]+=298.0.

Workup

  1. temperaturewas refluxed until a clear solution
  2. customformed
  3. additionAfter completion of the addition, analysis by HPLC/MS
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was triturated with a mixture of water (50 mL) and EtOAc (50 mL)
  6. filtrationfiltered
  7. customto obtain a solid product which
  8. extractionThe filtrate was extracted with EtOAc (30 mL×3)
  9. washThe combined extracts were washed with aqueous saturated NaCl solution
  10. dry with materialdried (Na2SO4)
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. customThe residue was purified
  14. washeluted with a gradient of EtOAc (30-100%) in hexanes

Sources & evidence

ORD record
ord-6bf3d6f1fc7f40fda16750ea6fa05384
Source dataset
uspto-grants-2009_08
Patent number
US07572808B2

Reaction notes

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