Acetic Acid → N-hydroxy-1-oxo-1,2-dihydroisoquinoline-7-carboxamide

Participants

Reaction Conditions

Reaction Steps

A mixture of hydroxylamine hydrochloride (2.0 g, 29 mmol) in methanol (10 mL) was heated at 90° C. under a dry nitrogen atmosphere until homogeneous. To this heated solution was added a solution of potassium hydroxide (2.85 g, 50.8 mmol) in methanol (6 mL). A precipitate formed on mixing. After heating at 90° C. for 30 minutes, the mixture was cooled to rt and the solids were allowed to settle. The resulting solution was assumed to contain 1.7 M hydroxylamine.potassium salt and was carefully removed by syringe to exclude solids. An aliquot of the above solution (1.0 mL, 1.7 mmol) was added to a solution of methyl 1-oxo-1,2-dihydroisoquinoline-7-carboxylate (32.5 mg, 0.16 mmol) in methanol (1 mL). After stirring for 1 h at rt, excess reagent was quenched by the addition of acetic acid (0.20 mL, 3.52 mmol). The mixture was concentrated to dryness and the residue was twice co-evaporated with toluene. The crude product was purified by preparative HPLC to afford N-hydroxy-1-oxo-1,2-dihydroisoquinoline-7-carboxamide (12 mg, 37%). LC-MS: (FA) ES+ 205; 1H NMR (300 MHz, MeOD) δ 8.67 (d, J=1.5 Hz, 1H), 8.06 (dd, J=8.3, 1.9 Hz, 1H), 7.73 (d, J=8.4 Hz, 1H), 7.26 (d, J=7.1 Hz, 1H), 6.70 (d, J=7.3 Hz, 1H).

Provenance & Evidence