Isoamyl Nitrite → 5,8-dichloro-7-methoxy-3,4-dihydroisoquinolin-1(2H)-one

Participants

Reaction Steps

Isopentyl nitrite (20 mL, 0.149 mol) was added dropwise to a heated (55° C.) suspension of copper (II) chloride (40 g, 0.298 mol) and lithium chloride (38 g, 0.905 mol) in acetonitrile (500 mL). The mixture was stirred at that temperature for 5 minutes, then 8-amino-5-chloro-7-methoxy-3,4-dihydroisoquinolin-1(2H)-one (296d, 20 g, 0.089 mol) was added in portions. After the addition was complete, stirring was continued at 55° C. for 45 minutes. The reaction mixture was cooled to room temperature, quenched with saturated aqueous ammonium chloride (300 mL), and extracted with ethyl acetate (4×200 mL). The combined organic layers were washed with aqueous ammonium chloride (200 mL) and brine (100 mL), dried over sodium sulfate, and concentrated under vacuum to give crude 5,8-dichloro-7-methoxy-3,4-dihydroisoquinolin-1(2H)-one (296e, 20 g, 90% purity, 92% yield) as a brown solid. MS: 245 [M+1].

Provenance & Evidence