Hydroxyamine hydrochloride → 3-(Isoquinolin-6-yl)isoxazol-5-amine

Participants

Reaction Steps

To a solution of 3-(isoquinolin-6-yl)-3-oxopropanenitrile (2.1 g, 11 mmol) in 60 mL of EtOH was added sodium acetate (5.3 g, 64 mmol) and hydroxylamine hydrochloride (3.7 g, 54 mmol) in 60 mL of water. The mixture was heated to reflux. After 3 hours, the reaction mixture was cooled to room temperature and diluted with 300 mL of EtOAc. The mixture was transferred to a separatory funnel and washed three times with 50 mL of water and once with 50 mL of brine. The remaining liquid was dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (1 to 5% MeOH/CH2Cl2), affording 3-(isoquinolin-6-yl)isoxazol-5-amine (0.96 g, 42% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.35 (s, 1H), 8.56 (d, J=6.5 Hz, 1H), 8.36 (s, 1H), 8.19 (d, J=8.6 Hz, 1H), 8.04 (dd, J=1.4 Hz, 8.5 Hz, 1H), 7.91 (d, J=5.9 Hz, 1H), 6.92 (s, 2H), 5.60 (s, 1H).

Provenance & Evidence