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

Temperature

0 °C

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.

1. stirringstirred for 2 hours
2. stirringthe mixture was stirred for 30 minutes
3. customThe organic solvent was evaporated under reduced pressure
4. additionthe residue was poured into water
5. extractionextracted with ethyl acetate twice
6. washThe organic layer was washed with water twice
7. dry with materialdried over magnesium sulfate
8. additiontreated with activated carbon
9. filtrationThe insoluble was filtered off
10. customthe solvent was evaporated under reduced pressure
11. dissolutionThe residue was dissolved in ethyl acetate (300 ml)
12. additionwere added diethyl ether (600 ml) and H2O (6 ml)
13. stirringThe mixture was stirred at room temperature overnight
14. customthe precipitate was collected
15. washwashed with ethyl acetate—diethyl ether (1:4)
16. customdried under reduced pressure at room temperature

ORD record

ord-317fc78b7af5472c97d77f437793b0ff

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08513202B2