Formaldehyde → HCID 86685104, compound

Participants

Reaction Conditions

Reaction Steps

Crude (2S,3S,4S,5R,6S)-3,4,5-tribenzyloxy-6-[4-chloro-3-[[4-[2-(cyclopropoxy)ethoxy]phenyl]methyl]phenyl]-6-methoxy-tetrahydropyran-2-carbaldehyde 1e (1.3 g, 1.7 mmol) was dissolved in 15 mL 1,4-dioxane, followed by addition of 37% formaldehyde solution (2.6 mL, 34 mmol) and a solution of sodium hydroxide (204 mg, 5.1 mmol) in 5.1 mL water into the reaction mixture. The reaction mixture was stirred for 4 hours at 70° C., then cooled to 50° C. and stirred for 16 hours. The reaction mixture was extracted with ethyl acetate (20 mL×3) after 20 mL saturated sodium chloride solution were added. The organic extract was washed with saturated sodium bicarbonate solution (20 mL), saturated sodium chloride solution (20 mL), combined, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure. Then 20 mL of mixed solution (THF and MeOH, v:v=1:1) were added into the residue, before sodium borohydride (130 mg, 3.4 mmol) was added. The reaction mixture was stirred for 30 minutes and concentrated under reduced pressure. The residue was dissolved in ethyl acetate (50 mL) and partitioned. The organic extract was washed with saturated sodium chloride solution (10 mL×2), combined, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure, then the resulting residue was purified by silica gel chromatography with elution system B to obtain the title compound [(3S,4S,5R,6S)-3,4,5-tribenzyloxy-6-[4-chloro-3-[[4-[2-(cyclopropoxy)ethoxy]phenyl]methyl]phenyl]-2-(hydroxymethyl)-6-methoxy-tetrahydropyran-2-yl]methanol 1f (320 mg, colorless oil), yield: 23.7%.

Provenance & Evidence