Boron Trichloride → (1R,2S,3S,4R,5S)-5-[4-chloro-3 [(4-ethoxyphenyl)methyl]phenyl]-1-(1-hydroxybut-2-ynyl)-6,8-dioxabicyclo[3.2.1]octane-2,3,4-triol

Temperature

-78 °C

To a solution of 1-[(1R,2S,3S,4R,5S)-2,3,4-tribenzyloxy-5-[4-chloro-3[(4-ethoxyphenyl)methyl]phenyl]-6,8-dioxabicyclo[3.2.1]octan-1-yl]but-2-yn-1-ol 5a (0.71 g, 0.95 mmol) in dichloromethane (30 mL) was added dropwsie boron trichloride (9.5 mL, 9.5 mmol, 1 M in dichloromethane) at −78° C. The mixture was stirred at −78° C. for 2 hours. The reaction mixture was then stirred at room temperature for 3 hours and quenched with 5 mL of saturated aqueous sodium bicarbonate. The resulting mixture was extracted with ethyl acetate (50 mL×3). The combined organic layers were washed with water (20 mL×2) and then saturated aqueous sodium chloride (20 mL×2), dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by prep-HPLC to afford title compound as a pale yellow solid (42 mg, 10.0%, HPLC: 91.8%). The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 475[M+H]+; and 1H NMR (400 MHz, DMSO-d6) δ(ppm): 7.63 (d, 1H), 7.48 (m, 1H), 7.39 (m, 1H), 7.02 (m, 2H), 6.79 (m, 2H), 5.07 (d, 1H), 5.06 (d, 1H), 4.79 (d, 1H), 4.62 (d, 1H), 4.48 (t, 1H), 4.46 (d, 1H), 3.95 (m, 4H), 3.82 (m, 2H), 3.71 (m, 1H), 3.53 (m, 1H), 1.45 (s, 3H), 1.28 (t, 3H).

1. stirringThe reaction mixture was then stirred at room temperature for 3 hours
2. customquenched with 5 mL of saturated aqueous sodium bicarbonate
3. extractionThe resulting mixture was extracted with ethyl acetate (50 mL×3)
4. washThe combined organic layers were washed with water (20 mL×2)
5. dry with materialsaturated aqueous sodium chloride (20 mL×2), dried over anhydrous sodium sulfate
6. concentrationconcentrated in vacuo
7. customThe residue was purified by prep-HPLC

ORD record

ord-9cbff04b98764885b87f0e5b20736125

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09394329B2