2,4-Dichloropyridine → 4-(2-Chloro-pyridin-4-yloxy)-2-fluoro-3-methyl-phenylamine

Participants

Reaction Steps

Potassium tert-butoxide (3.5 g, 31 mmol) was added to a solution of 4-amino-3-fluoro-2-methyl-phenol (4.2 g, 30 mmol) in DMA, and stirred at RT for 0.5 h. A solution of 2,4-dichloropyridine (4.38 g, 30 mmol) in DMA was added and the mixture was heated at 100° C. overnight. The reaction mixture was concentrated in vacuo and the residue was dissolved in EtOAc (200 mL) and filtered through silica gel. The filter cake was washed with EtOAc, and the combined filtrates were concentrated in vacuo and purified by silica gel chromatography to give 4-(2-chloro-pyridin-4-yloxy)-2-fluoro-3-methyl-phenylamine (3.2 g, 42% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.21 (d, J=6.4 Hz, 1 H), 6.84 (d, J=2.0 Hz, 1H), 6.81 (dd, J=5.6, 2.4 Hz, 1 H), 6.67-6.65 (m, 2 H), 5.13 (s, 2 H), 1.91 (s, 3H); MS (ESI): m/z 253.2 [M+H]+.

Provenance & Evidence