4-Aminophenol → 4-(4-Aminophenoxy)-N-methylpicolinamide

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-aminophenol (1 g, 9.2 mmol) in DMF (20 mL) was added 1M potassium tert-butoxide in THF (9.7 mL, 9.7 mmol) at room temperature. After 2 h, (4-chloro(2-pyridyl))-N-methylcarboxamide (1.6 g, 9.2 mmol) and potassium carbonate (0.64 g, 4.6 mmol) were added and then the reaction mixture was heated to 80° C. for 6 h. After cooling, the reaction mixture was extracted with ethyl acetate (50 mL). The organic layer was washed with brine (20 mL), dried over magnesium sulfate. The solvent was removed in vacuo. The residue was purified by column chromatography to afford 4-(4-amino-phenoxy)-pyridine-2-carboxylic acid methylamide (2.2 g, 80%) as a light-brown solid. 1H NMR (400 MHz, DMSO-d6): δ 8.94 (s, 1H), 8.89 (s, 1H), 8.78 (q, J=5 Hz, 1H), 8.50 (d, J=6 Hz, 1H), 7.61-7.54 (m, 4H), 7.38 (d, J=3 Hz, 1H), 7.29 (d, J=9 Hz, 2H), 7.19-7.12 (m, 3H), 2.78 (d, J=5 Hz, 3H).

Provenance & Evidence