Methanesulfonic Acid → (2S,3R,4S,5S,6R)-2-(4-chloro-3-(phenoxymethyl)phenyl)-6-(hydroxymethyl)-2-methoxytetrahydro-2H-pyran-3,4,5-triol

Participants

Reaction Steps

To a solution of 4-bromo-1-chloro-2-(phenoxymethyl)benzene (10.0 g, 33.61 mmol) in dry Toluene (200 mL) and dry THF (100 L), nBuLi (33.61 mL, 53.77 mmol, 1.6 M solution in pentane) was added at −78° C. The reaction mixture was stirred at the same temperature for 15 min. A solution of (3R,4S,5R,6R)-3,4,5-tris((trimethylsilyl)oxy)-6-(((trimethylsilyl)oxy)methyl)tetrahydro-2H-pyran-2-one (18.80 g, 40.33 mmol, prepared following the procedure given in US20070049537) in dry toluene (170 mL) was introduced into it at the same temperature and stirred for another 3 h. After completion of the reaction as confirmed by TLC, water (90 mL) was added at the same temperature and allowed to stir while raising the temperature to r.t. The reaction mixture was diluted with ethyl acetate (200 mL) and the separated aqueous layer was discarded. The organic layer was dried over Na2SO4 and concentrated in vacuo. The residue obtained was dissolved in methanol (90 mL) and methanesulfonic acid (2.15 mL, 33.56 mmol) was added at 0° C. The temperature was raised to r.t. gradually and stirred for 16 h. The reaction was quenched by the addition of NEt3 (14 mL, 50.5 mmol) at 0° C. The volatiles were evaporated in vacuo and the residue obtained was dissolved in ethyl acetate (500 mL), washed with water (200 mL) and brine (200 mL) successively. The organic layer was dried over anhydrous Na2SO4 and volatiles were evaporated in vacuo. The residue obtained was purified by column chromatography (silica gel, 1:9 MeOH:DCM) to provide title compound (9.5 g, 68.8%).

Provenance & Evidence