To a stirred solution of 4-bromophthalaldehyde (1.6 g, 7.74 mmol, 1.0 eq.) in ethanol (20 mL) was added diethyl aminomalonate hydrochloride (1.63 g, 7.74 mmol, 1.0 eq.) and sodium ethanolate (3.9 mL, 11.61 mmol, 1.5 eq.) in turn, and the reaction mixture was stirred at 80 °C under nitrogen protection for 4 for 4 hours. After completion of the reaction, the mixture was cooled to room temperature and the reaction was quenched with saturated ammonium chloride solution. Subsequently, the reaction mixture was extracted with ethyl acetate (2 x 50 mL), the organic phases were combined and dried over anhydrous sodium sulfate. The organic phase was concentrated under reduced pressure to give the crude product. The crude products from the two experiments were combined and purified by fast column chromatography on silica gel, the eluent being a 15-25% ethyl acetate/hexane solvent mixture. The target fractions were collected and concentrated under reduced pressure to afford ethyl 7-bromoisoquinoline-3-carboxylate (1.2 g, 28% yield) as a brown solid. The product was characterized by 1H NMR (400 MHz, CDCl3): δ 1.49 (t, J=7.2Hz, 3H), 4.51-4.57 (m, 2H), 7.86 (s, 2H), 8.24 (s, 1H), 8.56 (s, 1H), 9.28 (s, 1H).
