Bromine → HCID 89573799, compound

Participants

Reaction Steps

Bromine (0.20 mL, 3.80 mmol) was added dropwise to a solution of rel-(4aR,10bS)-8-fluoro-10b-methyl-4,4a,5,10b-tetrahydrochromeno[4,3-d][1,3]thiazin-2-amine from step F6 (644 mg, 2.55 mmol), in acetic acid (20 mL) at rt. The mixture was stirred for 30 min. The reaction was poured onto ice. The slurry was made pH 3 upon slow addition of 50% NaOH/water. The aqueous mixture was made basic pH 7-8 by the addition of solid sodium bicarbonate. The aqueous layers were extracted with EtOAc. The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified using silica gel column chromatography (0.25%-10% MeOH/CHCl3) to afford rel-(4aR,10bS)-9-bromo-8-fluoro-10b-methyl-4,4a,5,10b-tetrahydrochromeno[4,3-d][1,3]thiazin-2-amine (667 mg, 1.62 mmol, 64% yield) as a viscous oil. LCMS (M+H)+=333.02. 1H NMR (500 MHz, methanol-d4) δ 7.73 (d, J=7.5 Hz, 1H), 6.79 (d, J=9.8 Hz, 1H), 4.53 (dd, J=11.9, 2.9 Hz, 1H), 4.30 (dd, J=12.0, 6.0 Hz, 1H), 3.50 (dd, J=13.7, 3.9 Hz, 1H), 3.23 (dd, J=13.6, 8.1 Hz, 1H), 2.64 (dtd, J=10.0, 3.9, 3.0 Hz, 1H), 1.80 (s, 3H).

Provenance & Evidence