Dimethyl Sulfoxide → N-[(4aR,6R,8aS)-8a-(5-bromo-2-fluorophenyl)-6-formyl-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide

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Reaction Steps

Triethylamine (6.94 mL, 50.0 mmol), dimethyl sulfoxide (4.14 mL, 58.3 mmol) and pyridine-sulfur trioxide complex (5.41 g, 33.3 mmol) were added to a solution of N-[(4aR,6R,8aS)-8a-(5-bromo-2-fluorophenyl)-6-(hydroxymethyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide (C33) (2.00 g, 4.17 mmol) in dichloromethane (420 mL). The resulting solution was allowed to stir at room temperature for 16 hours. The reaction mixture was diluted with water (200 mL) and brine (200 mL). The resulting biphasic solution was left stirring at room temperature for 10 minutes. The organic layer was then isolated and the resulting aqueous layer was back extracted with dichloromethane (3×100 mL). The combined organics were washed with water (2×200 mL), aqueous 0.2 N hydrochloric acid (200 mL) and brine (200 mL), dried over sodium sulfate, filtered and concentrated. Purification via silica gel chromatography (Gradient: 20% to 100% ethyl acetate in heptane) afforded the product as a white solid. Yield 1.10 g, 55%. 1H NMR (400 MHz, DMSO-d6) characteristic peaks: δ 9.60 (s, 1H), 8.10 (br d, J=7.6 Hz, 2H), 7.47-7.67 (m, 5H), 7.32 (dd, J=12.1, 8.8 Hz, 1H), 4.32 (d, J=9.8 Hz, 1H), 3.07-3.11 (m, 1H), 2.67-2.88 (m, 2H), 1.96-2.00 (m, 1H), 1.67-1.74 (m, 1H).

Provenance & Evidence