2-(Dimethylamino)ethanol → 2-BROMO-4,5-DIMETHYLPYRIDINE

HRID 1913188Notes

Reaction equation

HRID 1913188 reaction equation
CN(C)CCO.C([Li])CCC.[N:12]1[CH:17]=[CH:16][C:15]([CH3:18])=[C:14]([CH3:19])[CH:13]=1.C(Br)(Br)(Br)[Br:21].BrC1C(C)=C(C)C=CN=1>CCCCCC.C1COCC1.O>[Br:21][C:17]1[CH:16]=[C:15]([CH3:18])[C:14]([CH3:19])=[CH:13][N:12]=1

Participants

9

Reactant 5

HCID 79022-(Dimethylamino)ethanolHCID 11205Carbon tetrabromideHCID 114173,4-DimethylpyridineHCID 218222912-Bromo-3,4-dimethylpyridineHCID 178418339Butyllithium

Product 1

HCID 110414352-BROMO-4,5-DIMETHYLPYRIDINE

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent2×

Conditions

Temperature
0 °C

Procedure

71.3 g (0.8 mol) of 2-(dimethylamino)ethanol are initially charged in 500 ml of n-hexane, and the mixture is cooled to 0° C. 1.0 liter (1.6 mol) of n-butyllithium solution (1.6 M in n-hexane) is added slowly, and the mixture is stirred at 0° C. for 15 min. A solution of 17.9 g (166.7 mmol) of 3,4-lutidine in 500 ml of n-hexane is then added dropwise, and the mixture is stirred at 0° C. for 1 h. The mixture is then cooled to −78° C., and a solution of 331.7 g (1.0 mol) of carbon tetrabromide in 1.0 liter of THF is added. The reaction mixture is stirred at −78° C. for 1 h and then allowed to warm to RT. The mixture is cooled again to 0° C., and 1.5 liters of water are slowly added dropwise. The phases are separated, and the organic phase is washed with water, dried over magnesium sulfate and concentrated under reduced pressure. The residue is initially prepurified on about 1 kg of silica gel (mobile phase: cyclohexane/ethyl acetate 9:1, then 7:3). The product-containing fractions are combined and concentrated under reduced pressure. The residue is then purified again on silica gel (mobile phase: cyclohexane/ethyl acetate 9:1). The product obtained in this manner contains about 10% of the regioisomeric 2-bromo-3,4-dimethylpyridine.

Workup

  1. stirringthe mixture is stirred at 0° C. for 1 h
  2. temperatureThe mixture is then cooled to −78° C.
  3. stirringThe reaction mixture is stirred at −78° C. for 1 h
  4. temperatureto warm to RT
  5. temperatureThe mixture is cooled again to 0° C.
  6. customThe phases are separated
  7. washthe organic phase is washed with water
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated under reduced pressure
  10. concentrationconcentrated under reduced pressure
  11. customThe residue is then purified again on silica gel (mobile phase: cyclohexane/ethyl acetate 9:1)
  12. customThe product obtained in this manner

Sources & evidence

ORD record
ord-a8e9117f91804ec4a09e5dfb3baf6fe0
Source dataset
uspto-grants-2013_12
Patent number
US08609698B2

Reaction notes

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