Hydrogen Bromide → 5-bromo-8-chloro-7-(propan-2-yloxy)-3,4-dihydroisoquinolin-1(2H)-one

Participants

Reaction Steps

To a solution of tert-butyl [8-chloro-1-oxo-7-(propan-2-yloxy)-1,2,3,4-tetrahydroisoquinolin-5-yl]carbamate (77c, 500 mg, 0.282 mmol) in THF (20 mL) was added HBr (10.0 mL, 88.4 mmol, 48% aqueous solution). The resulting mixture was stirred at room temperature for 3 hours. The reaction mixture was cooled to 0° C., CuBr (303 mg, 2.11 mmol) was added, followed by addition of NaNO2 (1.07 mL, 1.55 mmol, 100 mg/mL solution). The resulting reaction mixture was stirred at 0° C. for 1.5 hours. The reaction mixture was neutralized with NaHCO3 and extracted with ethyl acetate (2×50 mL). The combined organic phases were washed with brine (1×100 mL), dried over sodium sulfate, concentrated under vacuum, and purified by column chromatography (0-100% EtOAc/heptanes) to give 5-bromo-8-chloro-7-(propan-2-yloxy)-3,4-dihydroisoquinolin-1(2H)-one (77d, 188 mg, 42% over two steps) as a solid.

Provenance & Evidence