Citric Acid → HCID 22175437, compound

Participants

Reaction Steps

To a mixture of 3-{[(tert-butoxycarbonyl)amino]methyl}-2-isobutyl-1-oxo-4-phenyl-1,2-dihydro-6-isoquinolinecarboxylic acid (0.81 g, 1.8 mmol), N,O-dimethylhydroxylamine hydrochloride (0.211 g, 2.16 mmol), 1-hydroxy-1H-benzotriazole monohydrate (0.365 g, 2.7 mmol), 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (0.517 g, 2.7 mmol) and N,N-dimethylformamide (10 mL) was added triethylamine (0.301 mL, 2.16 mmol), and the mixture was stirred at room temperature for 17 h. The reaction mixture was poured into 0.1 M aqueous citric acid solution (100 mL) and extracted 3 times with ethyl acetate (50 mL). The organic layers were combined, washed once with 0.1 M aqueous citric acid solution (50 mL), twice with saturated aqueous sodium hydrogencarbonate (50 mL) and once with saturated brine (50 mL), dried over anhydrous magnesium sulfate (15 g), and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=3:4 (v/v)) to give tert-butyl(2-isobutyl-6-{[methoxy(methyl)amino]carbonyl}-1-oxo-4-phenyl-1,2-dihydro-3-isoquinolinyl)methylcarbamate (0.83 g, 94%) as a colorless, solid.

Provenance & Evidence