Hydrogen Peroxide → (S)-4-[(S)-1-(2,6-difluoropyridin-3-yl)ethyl]-2-hydroxy-6-methylmorpholin-3-one

Participants

Reaction Steps

A 1 M solution of lithium tri-sec-butylborohydride in THF (20 mL) was added dropwise to a solution of (S)-4-[(S)-1-(2,6-difluoropyridin-3-yl)ethyl]-6-methylmorpholine-2,3-dione (4.5 g) in THF at −50° C. or less, and the reaction solution was stirred for two hours. A 5 N sodium hydroxide solution (1.66 mL) and 30% aqueous hydrogen peroxide (6.78 mL) were added dropwise to the reaction solution at −10° C. or less, and the reaction solution was stirred for one hour. Sodium bisulfite (520 mg) was added to the reaction solution, which was then stirred for 30 minutes. Brine and 50% toluene-THF were added to the reaction solution, and the organic layer was separated. The aqueous layer was washed with 50% toluene-THF. The organic layers were combined and concentrated under reduced pressure. The residue was purified by column chromatography using a silica gel (heptane:ethyl acetate=1:1 to 0:100) to obtain 4.52 g of the title compound.

Provenance & Evidence