Hydrogen Bromide → 5-bromo-8-chloro-7-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)-3,4-dihydroisoquinolin-1(2H)-one

Participants

Reaction Steps

To a solution of 5-amino-8-chloro-7-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)-3,4-dihydroisoquinolin-1(2H)-one (293 g, 300 mg, 1.03 mmol) in tetrahydrofuran (5 mL) chilled in an ice-water bath was added 40% aqueous hydrobromic acid (6.86 g, 33.93 mmol). The mixture was allowed to stir at room temperature for three hours, and then cooled again to 0° C. Copper (I) bromide (295 mg, 2.06 mmol) was added, followed by sodium nitrite (78 mg, 1.13 mmol), and the resulting mixture stirred at 0° C. for two hours. The mixture was neutralized with solid sodium hydroxide and extracted with ethyl acetate (2×100 mL). The combined organic extracts were dried over sodium sulfate, concentrated, and purified by silica gel chromatography to give 5-bromo-8-chloro-7-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)-3,4-dihydroisoquinolin-1(2H)-one (293h, 60 mg, 16.5% yield) as a white solid.

Provenance & Evidence