Water → N-((4aS,5S,7aS)-7a-(2,4-Difluorophenyl)-5-(hydroxymethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl)benzamide

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Reaction Steps

N-((4aS,5S,7aS)-7a-(2,4-Difluorophenyl)-5-((trityloxy)methyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl)benzamide (3.99 g, 6.169 mmol) was taken up in formic acid (12 mL) at RT. The mixture was stirred at RT for 2.5 hours, then water (12 mL) was added. The mixture was stirred for 10 minutes and then filtered—washing with formic acid/water (1:1, 20 mL). The filtrate was evaporated and the residue was azeotroped with toluene (×2). The residue was taken up in dry MeOH (20 mL) and treated with potassium carbonate (1.0 g, 7.2 mmol). The mixture was stirred at RT for 30 minutes. The volatiles were removed in vacuo and the residue was partitioned between DCM and water. The layers were separated and the aqueous layer was further extracted with DCM (×4). The combined extracts were dried (Na2SO4), filtered and evaporated. The residue was purified by column chromatography (normal phase, 50 g, Biotage SNAP cartridge KP-Sil, 50 mL per min, gradient 40% to 90% EtOAc in n-hexane) to give the title compound (2.23 g). 1H NMR (400 MHz, MeOH-d4) δ ppm: 2.85-3.05 (m, 1 H) 3.10-3.27 (m, 2 H) 3.68-3.80 (m, 2 H) 4.02 (br. d, J=7.90 Hz, 1 H) 4.36-4.43 (m, 1 H) 4.47 (d, J=9.16 Hz, 1 H) 6.95-7.13 (m, 2 H) 7.39-7.50 (m, 2 H) 7.50-7.60 (m, 2 H) 7.96-8.16 (m, 2 H)

Provenance & Evidence