Boron trifluoride → (1S)-1,5-Anhydro-1-(3-((5-(4-fluorophenyl)-2-thienyl)methyl)-4-methylphenyl)-D-glucitol hemihydrate

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Reaction Conditions

Reaction Steps

A solution of 3 (63.1 g) and triethylsilane (46.4 g) in dichloromethane (660 ml) was cooled by dry ice—acetone bath under argon atmosphere, and thereto was added dropwise boron trifluoride.ethyl ether complex (50.0 ml), and the mixture was stirred at the same temperature. The mixture was allowed to warm to 0° C. and stirred for 2 hours. At the same temperature, a saturated aqueous sodium hydrogen carbonate solution (800 ml) was added, and the mixture was stirred for 30 minutes. The organic solvent was evaporated under reduced pressure, and the residue was poured into water and extracted with ethyl acetate twice. The organic layer was washed with water twice, dried over magnesium sulfate and treated with activated carbon. The insoluble was filtered off and the solvent was evaporated under reduced pressure. The residue was dissolved in ethyl acetate (300 ml), and thereto were added diethyl ether (600 ml) and H2O (6 ml). The mixture was stirred at room temperature overnight, and the precipitate was collected, washed with ethyl acetate—diethyl ether (1:4) and dried under reduced pressure at room temperature to give 1-(β-D-glucopyranosyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienylmethyl]benzene hemihydrate (33.5 g) as colorless crystals. mp 98-100° C. APCI-Mass m/Z 462 (M+NH4). 1H-NMR (DMSO-d6) δ 2.26 (3H, s), 3.13-3.28 (4H, m), 3.44 (1H, m), 3.69 (1H, m), 3.96 (1H, d, J=9.3 Hz), 4.10, 4.15 (each 1H, d, J=16.0 Hz), 4.43 (1H, t, J=5.8 Hz), 4.72 (1H, d, J=5.6 Hz), 4.92 (2H, d, J=4.8 Hz), 6.80 (1H, d, J=3.5 Hz), 7.11-7.15 (2H, m), 7.18-7.25 (3H, m), 7.28 (1H, d, J=3.5 Hz), 7.59 (2H, dd, J=8.8, 5.4 Hz). Anal. Calcd. for C24H25FO5S.0.5H2O: C, 63.56; H, 5.78; F, 4.19; S, 7.07. Found: C, 63.52; H, 5.72; F, 4.08; S, 7.00.

Provenance & Evidence