Trifluoromethanesulfonic acid → HCID 86685418, compound

Participants

Reaction Conditions

Reaction Steps

Triflic acid (0.25 mL, 2.82 mmol) was added to flask charged with a stirred solution of (7-bromo-1-methyl-3,4-dihydronaphthalen-2-yl)methyl carbamimidothioate from step C3 (255 mg, 0.819 mmol) in TFA (2.5 mL) at 0° C. The resulting mixture was capped and left to stir at 0° C. for 2 h. The reaction contents were carefully added to a swirled mixture of ice and excess solid sodium bicarbonate. After gas evolution had ceased, the resulting mixture was extracted with EtOAc. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo to afford rel-(4aS,10bR)-9-bromo-10b-methyl-4a,5,6,10b-tetrahydro-4H-naphtho[1,2-d][1,3]thiazin-2-amine as a white solid. The crude product was dissolved in THF (2.5 mL). Triethylamine (0.457 mL, 3.28 mmol), di-tert-butyl dicarbonate (0.571 mL, 2.458 mmol), and DMAP (5.00 mg, 0.041 mmol) were added to the crude product. After 16 h, the reaction mixture was concentrated in vacuo and purified using silica gel column chromatography (10:1 hexanes/EtOAc) to afford tert-butyl rel-((4aS,10bS)-9-bromo-10b-methyl-4a,5,6,10b-tetrahydro-4H-naphtho[1,2-d][1,3]thiazin-2-yl)carbamate (244 mg, 0.581 mmol, 71.0% yield) as a white solid. LCMS (M+H)+=225.0. 1H NMR (500 MHz, chloroform-d) δ 7.61 (br. s., 1H), 7.32 (dd, J=8.2, 1.8 Hz, 1H), 6.98 (d, J=8.2 Hz, 1H), 3.04 (dd, J=12.9, 3.6 Hz, 1H), 2.88 (dd, J=13.0, 8.2 Hz, 1H), 2.83 (t, J=6.9 Hz, 2H), 2.36-2.20 (m, 1H), 2.19-2.08 (m, 1H), 2.04-1.95 (m, 1H), 1.62 (s, 3H), 1.49 (s, 9H).

Provenance & Evidence