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

Temperature

80 °C

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).

1. temperatureAfter cooling
2. extractionthe reaction mixture was extracted with ethyl acetate (50 mL)
3. washThe organic layer was washed with brine (20 mL)
4. dry with materialdried over magnesium sulfate
5. customThe solvent was removed in vacuo
6. customThe residue was purified by column chromatography

ORD record

ord-2a8ba8081a874d588aa8e1caff4b1938

Source dataset

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09029401B2