Methanesulfonic Acid → (2S,3R,4S,5S,6R)-2-[4-chloro-3-[[4-(2,2-difluoroethoxy)phenyl]methyl]phenyl]-6-(hydroxymethyl)-2-methoxy-tetrahydropyran-3,4,5-triol

Participants

Reaction Conditions

Reaction Steps

Under Ar protection, 4-bromo-1-chloro-2-[[4-(2,2-difluoroethoxy)phenyl]methyl]benzene 12p (26.5 g, 73.3 mmol), MTBE (266 mL) and n-hexane (133 mL) were added into a 1 L reaction flask, stirred uniformly and cooled to −78° C., followed by dropwise addition of 2.4 M nBuLi (52 mL, 124.6 mmol) in 30 minutes. After stirring for 50 minutes at −78° C., a mixed solution of (3R,4S,5R,6R)-3,4,5-tris(trimethylsilyloxy)-6-(trimethylsilyloxymethyl)tetrahydropyran-2-one 2f (55 g, 117.3 mmol) in MTBE and n-hexane (60 mL:30 mL) was added within 20 minutes at −78° C. before the reaction mixture was stirred for 4 hours at −78° C. Thereafter, 130 mL methanol were added before stirring for 20 minutes. Then the reaction mixture was warmed to room temperature and stirred for 16 hours after methanesulfonic acid (25 g, 256.55 mmol) was added. 500 mL saturated sodium bicarbonate were added to the reaction mixture, stirred for 1 hour and partitioned. The aqueous phase was extracted with MTBE (100 mL×2) and the organic extract was combined, concentrated and purified by column chromatography (eluant: dichloromethane: methanol=100:1˜10:1) to obtain the title compound (2S,3R,4S,5S,6R)-2-[4-chloro-3-[[4-(2,2-difluoroethoxy)phenyl]methyl]phenyl]-6-(hydroxymethyl)-2-methoxy-tetrahydropyran-3,4,5-triol 12e (5 g, pale yellow solid), yield: 10%. MS m/z (ESI): 492.46 [M+18].

Provenance & Evidence