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

Participants

Reaction Conditions

Reaction Steps

A solution of 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 (2.2 g, 5.44 mmol) in dry THF (40 mL) under nitrogen was cooled to 0° C. Triethylamine (4.55 mL, 32.6 mmol), triethylamine tri-hydrogen fluoride (1.77 mL, 10.9 mmol) and nonafluorobutanesulfonyl fluoride (1.95 mL, 10.9 mmol) were then added. The colourless solution was stirred at 0° C. for 10 minutes and then removed from the ice bath. After 120 minutes at RT, the reaction was quenched with saturated aqueous NaHCO3 (25 mL). The THF was removed in vacuo and then the mixture was partitioned between EtOAc and water. The layers were separated and the aqueous layer was further extracted with EtOAc (×2). The combined extracts were washed with brine (×1), then dried (Na2SO4), filtered and evaporated. The residue was treated with DCM (˜20 mL) to give a gelatinous precipitate. This mixture was filtered (washing with DCM). The filtrate was concentrated to ˜3 mL and loaded directly on to the column and purified by chromatography (normal phase, 50 g, Biotage SNAP cartridge KP-Sil, 50 mL per mm, gradient 5% to 35% n-hexane in EtOAc) to give the title compound (1.45 g). 1H NMR (400 MHz, MeOH-d4) δ ppm: 2.97 (br. d, J=13.00 Hz, 1 H) 3.10-3.28 (m, 2 H) 4.02 (br. s., 1 H) 4.45-4.61 (m, 3 H) 4.62-4.71 (m, 1 H) 6.98-7.12 (m, 2 H) 7.40-7.51 (m, 2 H) 7.51-7.62 (m, 2 H) 8.03 (br. s., 2 H).

Provenance & Evidence