Trifluoromethanesulfonic acid → Trifluoroacetic acid

Participants

Reaction Steps

Triflic acid (1.33 mL, 15.0 mmol) was added to flask charged with a stirred solution of (2-bromo-9-methyl-6,7-dihydro-5H-benzo[7]annulen-8-yl)methyl carbamimidothioate, HCl from step E3 (540 mg, 1.5 mmol) in TFA (5.0 mL) at 0° C. The reaction mixture was allowed to warm to rt and stir for 6 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 ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The crude product was purified using preparatory HPLC (SunFire PrepC18 OBD 10 mm, 50×250 mm column, 90% MeOH/10% water/0.1% TFA-90% MeOH/10% water/0.1% TFA, linear gradiant over 34 min, 50 ml/min) to afford (4aS,11bS)-10-bromo-11b-methyl-4,4a,5,6,7,11b-hexahydrobenzo[6,7]cyclohepta[1,2-d][1,3]thiazin-2-amine, TFA (77 mg, 0.18 mmol, 12% yield) as a white solid. LCMS (M+H)+=327.0. 1H NMR (500 MHz, methanol-d4) δ 7.43 (dd, J=8.1, 2.1 Hz, 1H), 7.26 (d, J=2.1 Hz, 1H), 7.20 (d, J=8.1 Hz, 1H), 3.17-3.06 (m, 1H), 2.96 (dd, J=12.1, 3.1 Hz, 1H), 2.89 (dd, J=15.4, 5.6 Hz, 1H), 2.80 (t, J=12.4 Hz, 1H), 2.57-2.39 (m, 2H), 2.08 (dd, J=14.8, 4.0 Hz, 1H), 1.94-1.86 (m, 1H), 1.84 (s, 3H), 1.67-1.48 (m, 1H).

Provenance & Evidence