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

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.

1. stirringthe reaction solution was stirred for one hour
2. stirringwas then stirred for 30 minutes
3. customthe organic layer was separated
4. washThe aqueous layer was washed with 50% toluene-THF
5. concentrationconcentrated under reduced pressure
6. customThe residue was purified by column chromatography

ORD record

ord-59a048d97c5a43e3911dd49b382d20fb

Source dataset

uspto-grants-2009_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07618960B2