Sulfuric Acid → 7-Bromo-4-methylquinoline

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

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.