[Synthesis]
Concentrated sulfuric acid (14.4 mL, 270 mmol) was slowly added to a 1,4-dioxane (1 L) solution of 3-bromoaniline (30.0 g, 174 mmol) at room temperature. The reaction mixture was heated to reflux and a 1,4-dioxane (50 mL) solution of methyl vinyl ketone (19.5 mL, 270 mmol) was added dropwise over 3 hours. After the dropwise addition, the reflux reaction was continued for 1 hour. Upon completion of the reaction, the solvent was removed by distillation under reduced pressure. The residue was dissolved in water (100 mL), neutralized with sodium carbonate to neutral, and subsequently extracted with dichloromethane. The organic phases were combined, washed sequentially with water and saturated saline, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and the resulting crude product was purified by silica gel column chromatography (Biotage system, eluent 20% ethyl acetate/hexane) to afford 4-methyl-7-bromoquinoline (15.0 g, 43% yield) as a brown solid.1H NMR (CDCl3) δ: 8.80-8.75 (m, 1H), 8.30 (s, 1H), 7.90-7.85 (m , 1H), 7.70-7.65 (m, 1H), 7.25-7.20 (m, 1H), 2.65 (s, 3H). |