The general procedure for the synthesis of 4-bromo-1-chloroisoquinolines from 4-bromo-1(2H)-isoquinolinones was as follows: 4-bromoisoquinolin-1-ol (1.4 g, 5.80 mmol) was mixed with phosphorus trichloride (POCl3, 8.9 g, 58.09 mmol, 10 equiv.) and heated to reflux under stirring conditions. The progress of the reaction was monitored by liquid chromatography-mass spectrometry (LCMS) and it was confirmed that the reaction was completed after 4 hours. The reaction mixture was cooled to room temperature and the reaction was quenched with ice water (100 mL) followed by extraction with ethyl acetate (EtOAc, 3 x 25 mL). The organic phases were combined and washed sequentially with water (3 × 20 mL), saturated aqueous sodium bicarbonate (30 mL) and brine (20 mL). The organic layer was dried with anhydrous sodium sulfate and concentrated under reduced pressure to remove the solvent to afford 4-bromo-1-chloroisoquinoline as a white solid 1.3 g in 87% yield.
