Benzamide, 2-amino-4-hydroxy- (9CI)

38487-91-1

82049-00-1

Step A: 2-Amino-4-methoxybenzamide (7.0 g, 42 mmol) was dissolved in 1,2-dichloroethane (100 mL) at room temperature and boron tribromide (25 g, 100 mmol) was added slowly. The reaction mixture was heated to 40 °C and maintained for 20 hours. Subsequently, a tetrahydrofuran (THF) solution (40 mL) of 1N boron tribromide was added and the reaction temperature was raised to 50 °C and continued for 20 hours. Upon completion of the reaction, the mixture was cooled to room temperature and quenched by slow addition of aqueous sodium bicarbonate. The precipitated white solid, 2-amino-4-hydroxybenzamide (2.0 g) was collected by filtration. The mother liquor was concentrated, diluted with methanol (MeOH) and filtered and concentrated again. The residue was redissolved in methanol, filtered and concentrated, and finally purified by silica gel column chromatography using a gradient elution with 5-15% methanol/dichloromethane (MeOH/DCM) to give additional 2-amino-4-hydroxybenzamide white solid (4.7 g). The two obtained products were combined in a total yield of 6.7 g (quantitative yield). The product was characterized by 1H NMR (300 MHz, DMSO-d6) and LC-MS (ESI): 1H NMR δ 5.91 (dd, J = 8.67, 2.26 Hz, 1H), 6.03 (d, J = 2.45 Hz, 1H), 6.62 (br.s, 2H), 7.38 (d, J = 8.67 Hz, 1H), 9.45 (s , 1H); LC-MS (ESI) m/z 153 (M + H)+.