Hydrogen Bromide → 8-bromo-6-methoxyquinoline

HRID 987572Notes

Reaction equation

HRID 987572 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[C:11](N)[CH:12]=1)[N:9]=[CH:8][CH:7]=[CH:6]2.O.CCOC(C)=O.[BrH:21]>>[Br:21][C:11]1[CH:12]=[C:3]([O:2][CH3:1])[CH:4]=[C:5]2[C:10]=1[N:9]=[CH:8][CH:7]=[CH:6]2

Participants

5

Reactant 4

HCID 260Hydrogen Bromide2×HCID 962WaterHCID 70236-Methoxy-8-quinolinamineHCID 8857Ethyl Acetate

Product 1

HCID 2795998-bromo-6-methoxyquinolineYield 61%

Conditions

Temperature
0 °C

Procedure

To 5.05 g (29.0 mmol) 6-methoxy-quinolin-8-yl-amine in 25 mL of 48% HBr at 0° C. is added a solution of 2.60 g (37.7 mmol) and 20 mL H2O. After stirring at 0° C. for 15 min, the resulting mixture is added dropwise to a 75° C. solution of 5.0 g (34.8 mmol) CuBr and 60 mL of 48% HBr. After 5.5 h, the reaction mixture is neutralized with 150 mL of ice cold 5N NaOH, the resulting mixture is stirred with 300 mL EtOAc and filtered through a pad of celite. This mixture is extracted 2×100 mL EtOAc, and the combined organics are washed with 1×200 mL H2O, 1×200 mL brine, dried over Na2SO4, filtered, and the volatiles are evaporated. Flash chromatography on SiO2 gel, eluting with hexanes/EtOAc (4/1 to 1/1), gives 4.23 g (17.8 mmol, a 61% yield) of the title compound as a brown oil. MS (ES) m/z 239 (MH)+.

Workup

  1. waitAfter 5.5 h
  2. filtrationfiltered through a pad of celite
  3. extractionThis mixture is extracted 2×100 mL EtOAc
  4. washthe combined organics are washed with 1×200 mL H2O, 1×200 mL brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customthe volatiles are evaporated
  8. washFlash chromatography on SiO2 gel, eluting with hexanes/EtOAc (4/1 to 1/1)
  9. customgives 4.23 g (17.8 mmol

Sources & evidence

ORD record
ord-cb6e14c7a8914d30982d7723ab142908
Source dataset
uspto-grants-2003_10
Patent number
US06632824B2

Reaction notes

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