Methanesulfonic Acid → HCID 68015194, compound

Participants

Reaction Conditions

Reaction Steps

4-[(5-bromo-2-chloro-phenyl)methyl]-1-ethoxy-2-fluoro-benzene 4e (7.36 g, 21.4 mmol) was dissolved in 30 mL THF and cooled to −78° C., followed by dropwise addition of a solution of nBuLi in n-hexane (10.27 mL, 25.7 mmol). After stirring for 1 hour at −78° C., a solution (20 mL) of (3R,4S,5R,6R)-3,4,5-tris(trimethylsilyloxy)-6-(trimethylsilyloxymethyl)tetrahydropyran-2-one 2f (11 g, 23.6 mmol) in THF was added before the reaction mixture was stirred for 2 hours at −78° C. Then the reaction mixture was warmed and stirred for 16 hours at room temperature after 2.8 mL methylsulfonic acid and 71 mL methanol were added. Thereafter, the reaction mixture was concentrated under reduced pressure after 100 mL saturated sodium carbonate solution were added. The residue was dissolved in 50 mL saturated sodium chloride, extracted with ethyl acetate (100 mL×3). The organic extract was combined, dried over anhydrous magnesium sulfate, filtered. The filtrate was concentrated under reduced pressure and the resulting residue was purified by silica gel chromatography with elution system A to obtain the title compound (2S,3R,4S,5S,6R)-2-[4-chloro-3-[(4-ethoxy-3-fluoro-phenyl)methyl]phenyl]-6-(hydroxymethyl)-2-methoxy-tetrahydropyran-3,4,5-triol 4f (5.7 g, white solid), yield: 58.3%. 1H NMR (400 MHz, CD3OD): δ 7.56 (s, 1H), 7.48 (dd, 1H), 7.37 (dd, 1H), 6.95-6.87 (m, 3H), 4.08-4.07 (m, 4H), 3.91 (m, 1H), 3.93-3.73 (m, 2H), 3.56-3.53 (m, 1H), 3.45-3.43 (m, 1H), 3.30 (s, 2H), 3.08 (s, 3H), 1.35 (t, 3H).

Provenance & Evidence