Trifluoroacetic acid → 3-Bromo-5-(pyridin-3-ylamino)-phenol

Participants

Reaction Steps

[3-Bromo-5-(4-methoxy-benzyloxy)-phenyl]-pyridin-3-yl-amine (26.7 g, 69.2 mmol) was dissolved in thioanisole (62 mL, 529 mmol). Trifluoroacetic acid (81 mL, 1.06 mol) was added slowly with the temperature held between 20 and 25° C. over a period of 100 min. The solution was left to stand at room temperature for 2 hours. The reaction solution was diluted with water (100 mL) and concentrated to a small volume (˜30 mL). To the residue were added TBME (250 mL), water (300 mL) and methanol (30 mL). The organic layer was extracted with a mixture of 4N hydrochloric acid and methanol. The combined aqueous layers were diluted with methanol (100 mL), washed with methylene chloride (3×150 mL) and neutralized with 4N NaOH (440 mL) to pH 7. The precipitated white solid was collected, washed with cold water (2×10 mL) and dried in a vacuum oven overnight at 60° C. 3-Bromo-5-(pyridin-3-ylamino)-phenol (9.21 g, 50%) was obtained as an off white solid.

Provenance & Evidence