Sulfuric Acid → 7-Bromo-4-methylquinoline

HRID 1788332Notes

Reaction equation

HRID 1788332 reaction equation
OS(O)(=O)=O.[Br:6][C:7]1[CH:8]=[C:9]([CH:11]=[CH:12][CH:13]=1)[NH2:10].[CH:14]([C:16]([CH3:18])=O)=[CH2:15]>O1CCOCC1>[Br:6][C:7]1[CH:8]=[C:9]2[C:11]([C:16]([CH3:18])=[CH:14][CH:15]=[N:10]2)=[CH:12][CH:13]=1

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 6570Methyl vinyl ketoneHCID 115623-Bromoaniline

Product 1

HCID 219925517-Bromo-4-methylquinoline

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

H2SO4 (14.4 mL, 270 mmol) is added to a solution of 3-bromoaniline (Aldrich, 30.0 g, 174 mmol) in 1,4-dioxane (1 L) at RT. The mixture is heated to reflux and treated with methyl vinyl ketone (Aldrich, 19.5 mL, 270 mmol) in 1,4-dioxane (50 mL) dropwise over 3 h. Heating is continued for 1 h after the addition, followed by removal of the solvent in vacuo. The residue is dissolved in water (100 mL), neutralized with Na2CO3 and extracted with CH2Cl2. The combined organic extracts are washed with water and brine, dried (Na2SO4) and filtered. The filtrate is concentrated, and the residue chromatographed on silica gel (Biotage, eluting with 20% EtOAc/Hexanes) to give the title compound, 15.0 g (43%), as a brownish solid.

Workup

  1. temperatureThe mixture is heated
  2. temperatureto reflux
  3. temperatureHeating
  4. additionafter the addition
  5. customfollowed by removal of the solvent in vacuo
  6. dissolutionThe residue is dissolved in water (100 mL)
  7. extractionextracted with CH2Cl2
  8. washThe combined organic extracts are washed with water and brine
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. concentrationThe filtrate is concentrated
  12. customthe residue chromatographed on silica gel (Biotage, eluting with 20% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-8f57fa29e9ac49ff89af3b6a105da1ce
Source dataset
uspto-grants-2009_03
Patent number
US07511065B2

Reaction notes

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