Step 1: 1,4-Dihydro-3(2H)-isoquinolinone (206 mg, 1.38 mmol, 1.0 eq.) was slowly added to a mixture of POCl3 (0.73 mL, 7.85 mmol, 3.8 eq.) and DMF (0.6 g, 8.16 mmol, 4.0 eq.) in THF (10 mL) at 0 °C over 5 min. The reaction mixture was continued to be stirred at 0 °C for 1 h, followed by slow pouring into a pre-cooled mixture of 2N NaOH (20 mL), ice (20 g) and toluene (20 mL). The organic phase was separated and the aqueous phase was re-extracted with toluene (20 mL). The combined organic layers were washed with distilled water (20 mL), dried over anhydrous Na2SO4, and concentrated to half the original volume under reduced pressure at low temperature. Under vigorous stirring, 2N H2SO4 (20 mL) was slowly added to the concentrate, followed by the addition of KMnO4 (436 mg, 2.76 mmol, 2.0 eq.) in batches. The reaction mixture was continued to stir for 4 hours. The organic phase was separated, dried over anhydrous Na2SO4 and concentrated under reduced pressure to give 3-chloroisoquinoline-4-carbaldehyde (220 mg, 50% purity) as an oil, which was used directly in the next step of the reaction.LRMS (M+H+) m/z 192.0.
