Sodium Hydroxide → (RS)-2-(5-Bromo-6-methoxypyridin-3-yl)-1,1,1-trifluoropropan-2-ol

Participants

Reaction Conditions

Reaction Steps

Bromine (0.734 mL, 14.24 mmol) was added under nitrogen atmosphere to an acetic acid (20 mL, 349 mmol) mixture of (RS)-1,1,1-trifluoro-2-(6-methoxypyridin-3-yl)propan-2-ol (Step A, 2.1 g, 9.49 mmol) and potassium acetate (4.66 g, 47.5 mmol), which was then stirred for 30 minutes at 80° C. in oil bath. LCMS showed 30% conversion to product with a clean profile. The reaction was allowed to stir for 1.5 hours total at 80° C. and LCMS showed 40% conversion. Two additional bromine additions (0.734 mL, 14.24 mmol each) were added 30 minutes apart. The reaction was then allowed to stir at 25° C. for 48 hours. The reaction was 80% complete by LCMS. It was diluted with ethyl acetate and poured slowly into 5N NaOH (70.1 mL, 350 mmol) to neutralize the acetic acid. The organic layer was washed with brine (100 mL) and concentrated. Silica gel chromatography using a linear gradient of 0-100% ethyl acetate/hexanes gave the title compound as a pale yellow solid. LCMS (M+H)+: 302.2. 1H NMR (CDCl3, 500 MHz): δ 8.29 (d, J=1.8 Hz, 1H), 8.07 (d, J=1.8 Hz, 1H), 4.06 (s, 3H), 2.53 (s, 1H), 1.81 (s, 3H).

Provenance & Evidence