Dimethyl Sulfoxide → (2S,3S,4S,5R,6S)-3,4,5-tribenzyloxy-6-[4-chloro-3-[[4-(2,2-difluoro-ethoxy)phenyl]methyl]phenyl]-6-methoxy-tetrahydropyran-2-carbaldehyde

Participants

Reaction Conditions

Reaction Steps

Oxalyl chloride (0.18 mL, 2.16 mmol) was dissolved in 5 mL methylene chloride and cooled to −78° C., followed by dropwise addition of a solution (3 mL) of dimethyl sulfoxide (0.23 mL, 3.31 mmol) in methylene chloride, and the reaction mixture was stirred for 15 minutes. 10 mL solution of [(2R,3R,4S,5R,6S)-3,4,5-tribenzyloxy-6-[4-chloro-3-[[4-(2,2-difluoroethoxy)phenyl]methyl]phenyl]-6-methoxy-tetrahydropyran-2-yl]methanol 12h (1.23 g, 1.66 mmol) in methylene chloride were dropwise added before the mixture was stirred for 40 minutes. The reaction mixture was warmed to room temperature and stirred for 3 hours after triethylamine (1.2 mL, 8.31 mmol) was dropwise added. Thereafter, the reaction mixture was partitioned after 5 mL 1 M hydrochloric acid were added. The aqueous phase was extracted with ethyl acetate (20 mL×2) and the organic extract was combined, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure to obtain the title compound (2S,3S,4S,5R,6S)-3,4,5-tribenzyloxy-6-[4-chloro-3-[[4-(2,2-difluoro-ethoxy)phenyl]methyl]phenyl]-6-methoxy-tetrahydropyran-2-carbaldehyde 12i (1.10 g, yellow grease), which was used directly in the next step without purification.

Provenance & Evidence