Phosphorus oxybromide → 2-Bromo-4-methyl-5-nitropyridine

HRID 2377045Notes

Reaction equation

HRID 2377045 reaction equation
[CH3:1][C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][N:5]=[C:4](O)[CH:3]=1.P(Br)(Br)([Br:14])=O>ClCCl>[Br:14][C:4]1[CH:3]=[C:2]([CH3:1])[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][N:5]=1

Participants

4

Reactant 2

HCID 24613Phosphorus oxybromideHCID 178429283HCID 178429283, compound

Product 1

HCID 3458732-Bromo-4-methyl-5-nitropyridine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 4-methyl-5-nitropyridin-2-ol (82 g, 0.53 mol) and POBr3 (229 g, 0.8 mol, 1.5 eq.) in dichloromethane (2 L) was heated under a nitrogen atmosphere in a 3 L 3-neck flask with overhead stirrer for 24 h. The mixture was filtered cold. The solid consisted of a 1:1 mixture of desired product 2 and unreacted starting material 4-methyl-5-nitropyridin-2-ol, the filtrate contained the desired product and unreacted POBr3. The solid (46 g) and fresh POBr3 were dissolved in dichloromethane and refluxed for 10 h. The liquid was decanted and combined with the filtrate of the first reaction. The combined solutions were concentrated to a volume of 1.5 L. The mixture was cooled in an ice bath and stirred while ice (500 g) was added to quench the excess POBr3. The organic layer was separated, and the aqueous layer was extracted with dichloromethane. The combined organic extracts were dried (magnesium sulfate) and concentrated. The product was recrystallized from hexanes. Yield: 104 g (90%). 1H NMR (300 MHz, CDCl3) δ ppm 2.63 (s, 3H) 7.52 (s, 1H) 8.95 (s, 1H). LCMS: (APCI, M-H)=215 and 217 u/e (bromine isotope pattern); Retention Time: 3.01 min; Purity by TIC: 95%; Purity by UV: 95%.

Workup

  1. filtrationThe mixture was filtered cold
  2. additionThe solid consisted of a 1:1 mixture of desired product 2
  3. dissolutionThe solid (46 g) and fresh POBr3 were dissolved in dichloromethane
  4. temperaturerefluxed for 10 h
  5. customThe liquid was decanted
  6. customcombined with the filtrate of the first reaction
  7. concentrationThe combined solutions were concentrated to a volume of 1.5 L
  8. temperatureThe mixture was cooled in an ice bath
  9. additionwas added
  10. customto quench the excess POBr3
  11. customThe organic layer was separated
  12. extractionthe aqueous layer was extracted with dichloromethane
  13. dry with materialThe combined organic extracts were dried (magnesium sulfate)
  14. concentrationconcentrated
  15. customThe product was recrystallized from hexanes

Sources & evidence

ORD record
ord-cf526691501f4ec48eee42b21b737259
Source dataset
uspto-grants-2008_12
Patent number
US07468375B2

Reaction notes

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