Benzoyl Peroxide → 4,6-Dibromo-3-(bromomethyl)-2-(2-chloro-4-fluorophenyl)pyridine

HRID 394176Notes

Reaction equation

HRID 394176 reaction equation
[Br:1][C:2]1[CH:7]=[C:6]([Br:8])[N:5]=[C:4]([C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:10]=2[Cl:16])[C:3]=1[CH3:17].[Br:18]N1C(=O)CCC1=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>ClCCCl>[Br:1][C:2]1[CH:7]=[C:6]([Br:8])[N:5]=[C:4]([C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:10]=2[Cl:16])[C:3]=1[CH2:17][Br:18]

Participants

5

Reactant 3

HCID 7187Benzoyl PeroxideHCID 67184N-bromobutanimideHCID 226480084,6-Dibromo-2-(2-chloro-4-fluorophenyl)-3-methylpyridine

Product 1

HCID 226479624,6-Dibromo-3-(bromomethyl)-2-(2-chloro-4-fluorophenyl)pyridine

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 4,6-dibromo-2-(2-chloro-4-fluorophenyl)-3-methylpyridine (3.55 g, 9.35 mmol, 1 eq) in 1,2-dichloroethane (90 mL) was added N-bromosuccinimide (2.0 g, 11.22 mmol, 1.2 eq) and benzoyl peroxide (226 mg, 0.9 mmol, 0.1 eq). The resulting mixture was degassed with argon then warmed to and maintained at reflux for 5.5 h. The mixture was cooled solvent was removed under reduced pressure, and the material was purified by flash column chromatography eluting with 2% Et2O in hexanes. The material was re-dissolved in CCl4 and N-bromosuccinimide (667 mg) and benzoyl peroxide (75 mg) were added. The mixture was brought to and maintained at reflux for 6.5 h. The mixture was cooled to 0° C., filtered to remove the succinimide, and concentrated under reduced pressure. The product was purified by flash column chromatography on silica gel eluting with 2% Et2O in hexanes to give 4,6-dibromo-3-(bromomethyl)-2-(2-chloro-4-fluorophenyl)pyridine. Mass spectrum (ESI) 456.1 (M+1); 458.0 (M+3); 460.1 (M+5); 462.1 (M+7). 1H NMR (500 MHz, CDCl3) δCHCl3: 7.85 (1H, s); 7.46 (1H, dd, J=8.5 Hz, J=5.7 Hz); 7.27 (1H, dd, J=8.5 Hz, J=2.5 Hz); 7.16 (1H, ddd, J=8.5 Hz, J=8.3 Hz, J=2.5 Hz); 4.55 (1H, ½ ABq, J=10.8 Hz); 4.17 (1H, ½ ABq, J=10.8 Hz,

Workup

  1. customThe resulting mixture was degassed with argon
  2. temperaturethen warmed to and
  3. temperaturemaintained
  4. temperatureat reflux for 5.5 h
  5. temperatureThe mixture was cooled solvent
  6. customwas removed under reduced pressure
  7. customthe material was purified by flash column chromatography
  8. washeluting with 2% Et2O in hexanes
  9. dissolutionThe material was re-dissolved in CCl4
  10. additionN-bromosuccinimide (667 mg) and benzoyl peroxide (75 mg) were added
  11. temperaturemaintained
  12. temperatureat reflux for 6.5 h
  13. filtrationfiltered
  14. customto remove the succinimide
  15. concentrationconcentrated under reduced pressure
  16. customThe product was purified by flash column chromatography on silica gel eluting with 2% Et2O in hexanes

Sources & evidence

ORD record
ord-4669c42ee4a345c1b81f4ac5f1ef7926
Source dataset
uspto-grants-2004_10
Patent number
US06809199B2

Reaction notes

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