Phosphorus oxybromide → 2-Bromo-5-methyl-3-phenylimidazo[1,2-A]pyridine

HRID 872364Notes

Reaction equation

HRID 872364 reaction equation
[CH3:1][C:2]1[N:7]2[C:8]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[C:9](O)[N:10]=[C:6]2[CH:5]=[CH:4][CH:3]=1.P(Br)(Br)([Br:20])=O.C(=O)(O)[O-].[Na+]>ClCCCl>[Br:20][C:9]1[N:10]=[C:6]2[CH:5]=[CH:4][CH:3]=[C:2]([CH3:1])[N:7]2[C:8]=1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

5

Reactant 3

HCID 24613Phosphorus oxybromide2×HCID 516892Sodium BicarbonateHCID 666650655-Methyl-3-phenylimidazo[1,2-a]pyridin-2-ol

Product 1

HCID 666657172-Bromo-5-methyl-3-phenylimidazo[1,2-A]pyridineYield 53.4%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

5-Methyl-3-phenylimidazo[1,2-a]pyridin-2-ol from step 2 (1.30 g, 5.22 mmol) were dissolved in 41 mL 1,2-dichloroethane under argon atmosphere. 5 Equivalents of phosphoryl bromide (7.48 g, 26.1 mmol) were added and the reaction mixture was stirred at reflux temperature overnight. LC/MS analysis showed incomplete conversion, therefore another 5 equivalents phosphoryl bromide were added. After stirring for 4 h at reflux temperature LC/MS analysis again showed incomplete conversion, so 5 equivalents were added again. After stirring at reflux temperature overnight the reaction mixture was allowed to cool to room temperature. The reaction mixture was neutralized with aqueous sodium bicarbonate-solution followed by extraction with dichloromethane. The organic phase was washed with brine and filtered through a Whatman-filter. Drying under high vacuum gave 801 mg (44%) of the title compound in 83% purity (LC/MS, area-%).

Workup

  1. temperatureat reflux temperature overnight
  2. stirringAfter stirring for 4 h
  3. temperatureat reflux temperature LC/MS analysis again showed incomplete conversion
  4. additionso 5 equivalents were added again
  5. stirringAfter stirring
  6. temperatureat reflux temperature overnight the reaction mixture
  7. extractionfollowed by extraction with dichloromethane
  8. washThe organic phase was washed with brine
  9. filtrationfiltered through a Whatman-filter
  10. customDrying under high vacuum

Sources & evidence

ORD record
ord-03f010517e6248bf86c738ace6ee6aae
Source dataset
uspto-grants-2015_03
Patent number
US08975265B2

Reaction notes

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