Sodium Hydroxide → rel-(4aS,11bS)-10-bromo-11b-methyl-4a,5,6,11b-tetrahydro-4H-benzo[2,3]oxepino[4,5-d][1,3]thiazin-2-amine

Participants

Reaction Steps

To a solution of (7-bromo-5-methyl-2,3-dihydrobenzo[b]oxepin-4-yl)methyl carbamimidothioate hydrochloride from step H8 (2.59 g, 7.12 mmol) in TFA (20 mL) was added triflic acid (5.0 mL). The mixture was stirred at rt for 3 h. The reaction mixture was chilled to 0° C. then diluted with diethyl ether (150 mL). The resulting mixture was slowly neutralized with 50% aqueous NaOH and made basic (pH=12) with saturated aqueous NaHCO3 solution. The organic layer was separated, dried over sodium sulfate, filtered, and concentrated in vacuo. The crude material was purified by silica gel column chromography (30-100% EtOAc/hexanes) to afford rel-(4aS,11bS)-10-bromo-11b-methyl-4a,5,6,11b-tetrahydro-4H-benzo[2,3]oxepino[4,5-d][1,3]thiazin-2-amine (1.31 g, 4.00 mmol, 56% yield). LCMS (M+H)+=329.0. 1H NMR (500 MHz, methanol-d4) δ 7.50 (dd, J=8.5, 2.4 Hz, 1H), 7.18 (d, J=2.4 Hz, 1H), 7.05 (d, J=8.4 Hz, 1H), 4.38-4.31 (m, 1H), 3.76 (td, J=13.2, 1.5 Hz, 1H), 3.05-2.92 (m, 2H), 2.85 (ddt, J=15.5, 13.4, 4.5 Hz, 1H), 2.55-2.47 (m, 1H), 1.96-1.88 (m, 1H), 1.86 (s, 3H).

Provenance & Evidence