7-Bromo-3-chloroquinoline

59278-65-8

621-62-5

1246549-62-1

General procedure for the synthesis of 7-bromo-3-chloroquinoline from 2-amino-4-bromobenzaldehyde and chloroacetaldehyde diethyl acetal: 2-chloro-1,1-diethoxyethane (4.50 mL, 30.0 mmol), 2-amino-4-bromobenzaldehyde (3.00 g, 15.0 mmol), and p-toluenesulfonic acid monohydrate (0.285 g, 1.500 mmol) were dissolved in toluene (50 mL), assembled with a Dean-Stark manifold, and heated to reflux at 110 °C for 3 hours. Upon completion of the reaction, the solvent was evaporated under reduced pressure and the residue was dissolved in ethyl acetate and washed with saturated aqueous sodium bicarbonate. The aqueous layer was then extracted with ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate and concentrated to dryness. The crude product was purified by silica gel column chromatography with 20-50% dichloromethane/hexane as eluent to give the title compound 7-bromo-3-chloroquinoline (1.97 g, 8.12 mmol, 54% yield) as a yellow solid. Mass spectrum (ESI+) m/e 241.8/243.8 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ 7.85 (dd, J = 8.84, 2.02 Hz, 1H), 7.98 (d, J = 8.59 Hz, 1H), 8.29 (d, J = 1.77 Hz, 1H), 8.65 (d, J = 2.02 Hz, 1H), 8.94 (d, J = 2.53 Hz, 1H).