Formaldehyde → (2S,3S,4S,5R,6S)-3,4,5-tribenzyloxy-6-[4-chloro-3-[[4-(2,2-difluoroethoxy)phenyl]methyl]phenyl]-2-(hydroxymethyl)-6-methoxy-tetrahydropyran-2-carbaldehyde

Participants

Reaction Conditions

Reaction Steps

(2S,3S,4S,5R,6S)-3,4,5-tribenzyloxy-6-[4-chloro-3-[[4-(2,2-difluoroethoxy)phenyl]methyl]phenyl]-6-methoxy-tetrahydropyran-2-carbaldehyde 12i (1.10 g, 1.48 mmol) was dissolved in 20 mL 1,4-dioxane, followed by addition of 2.5 mL of 37% formaldehyde solution and dropwise addition of 4 mL of 2.9 M sodium hydroxide solution. The reaction mixture was stirred for 25 hours at 70° C. Thereafter, the reaction mixture was concentrated under reduced pressure before 20 mL water and 10 mL saturated sodium chloride solution were added. The aqueous phase was extracted with ethyl acetate (30 mL×3) 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-difluoroethoxy)phenyl]methyl]phenyl]-2-(hydroxymethyl)-6-methoxy-tetrahydropyran-2-carbaldehyde 12j (1.09 g, yellow grease), which was used directly in the next step without purification.

Provenance & Evidence