Sodium Hydroxide → 3-Amino-2-bromo-4,6-dimethylpyridine

HRID 1271570Notes

Reaction equation

HRID 1271570 reaction equation
Cl[C:2]1[C:7]([NH2:8])=[C:6]([CH3:9])[CH:5]=[C:4]([CH3:10])[N:3]=1.P(Br)(Br)[Br:12].[OH-].[Na+]>C1(C)C=CC=CC=1>[Br:12][C:2]1[C:7]([NH2:8])=[C:6]([CH3:9])[CH:5]=[C:4]([CH3:10])[N:3]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 24614Phosphorus tribromideHCID 105111202-Chloro-4,6-dimethylpyridin-3-amine

Product 1

HCID 20493073-Amino-2-bromo-4,6-dimethylpyridineYield 38%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of 1.80 g (11.0 mmol) of 2-chloro-4,6-dimethyl-pyridin-3-ylamine (prepared as described in J. M. Klunder et al. J. Med. Chem., 35, 1992, 1887-1897) in toluene (10 ml) was added PBr3 (18 ml). The reaction mixture was stirred for 48 h under reflux. After cooling the reaction mixture, it was poured onto ice, basified with NaOH 2 M solution (400 ml) and the aqueous phase was extracted twice with ethyl acetate. The combined organic phases were washed with brine, dried over Na2SO4, filtered and evaporated. The crude residue was purified by flash chromatography (cyclohexane/ethyl acetate 7:3) to yield 2.31 g (38%) of 2-bromo-4,6-dimethyl-pyridin-3-ylamine containing small amount of 2-chloro-4,6-dimethyl-pyridin-3-ylamine as a yellow oil.

Workup

  1. temperatureunder reflux
  2. temperatureAfter cooling the reaction mixture, it
  3. additionwas poured onto ice
  4. extractionthe aqueous phase was extracted twice with ethyl acetate
  5. washThe combined organic phases were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customevaporated
  9. customThe crude residue was purified by flash chromatography (cyclohexane/ethyl acetate 7:3)

Sources & evidence

ORD record
ord-9a6140d8aa2b41f19b7bf4fccb55939f
Source dataset
uspto-grants-2007_04
Patent number
US07205411B2

Reaction notes

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