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

A THF solution (20 mL) of 1 M lithium tri-s-butyl borohydride was dropwise added to a THF solution of (S)-4-[(S)-1-(2,6-difluoropyridin-3-yl)ethyl]-6-methylmorpholin-2,3-dione (4.5 g) at −50° C. or below. The resulting reaction solution was stirred for 2 hr. To the reaction solution, a 5 N sodium hydroxide aqueous solution (1.66 mL) and 30% hydrogen peroxide aqueous solution (6.78 mL) were added in this order at −10° C. or below. The resulting reaction solution was stirred for 1 hr, and then sodium hydrogensulfite (520 mg) was added thereto. The resulting reaction solution was stirred for 30 min, and then saturated saline and 50% toluene-THF were added thereto. The organic layer was separated, and the water layer was extracted with 50% toluene-THF. All the organic layers were combined and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (heptane:ethyl acetate=1:1 to 0:1) to give 4.52 g of the title compound. The physical property values of this compound were as follows:

1. customThe resulting reaction solution
2. customThe resulting reaction solution
3. stirringwas stirred for 1 hr
4. customThe resulting reaction solution
5. stirringwas stirred for 30 min
6. customThe organic layer was separated
7. extractionthe water layer was extracted with 50% toluene-THF
8. concentrationconcentrated under reduced pressure
9. customThe residue was purified by silica gel column chromatography (heptane:ethyl acetate=1:1 to 0:1)

ORD record

ord-e4add3c7b0cb46f892e2e022b2640d7e

Source dataset

uspto-grants-2010_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07737141B2