Dimethylformamide → 3-Chloroisoquinoline-4-carbaldehyde

Participants

Reaction Conditions

Reaction Steps

To a mixture of POCl3 (0.73 mL, 7.85 mmol, 3.8 eqiv.) and DMF (0.6 g, 8.16 mmol, 4.0 equiv.) in THF was added 1,2-dihydroisoquinolin-3-(4H)-one at 0° C. in portions for 5 min. The mixture was continued to stir at 0° C. for 1 h and poured into a mixture of 2 N NaOH (20 mL), ice (20 g), and toluene (20 mL). The organic phase was separated and the aqueous layer was extracted with toluene one more time. The combined organic layer was washed with water, dried over Na2SO4, and concentrated to half of its volume at low temperature in vacuo. To this mixture was added 2 N H2SO4 (20 mL) under vigorous stirring followed by ground KMnO4 in portions. The mixture was continued to stir for another 4 h. The organic phase was separated, dried over Na2SO4, and concentrated to give 3-chloroisoquinoline-4-carbaldehyde (220 mg, 50% pure) as a oil, which was used for next step without further purification. LRMS (M+H+) m/z 192.0.

Provenance & Evidence