Reaction #44619

Reaction equation

sodium hydrogensulfite

sodium hydroxide

hydrogen peroxide

lithium tri-s-butyl borohydride

(S)-4-[(S)-1-(2,6-difluoropyridin-3-yl)ethyl]-6-methylmorpholin-2,3-dione

→

title compound

Yield 99.7%

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

Yield 99.7%

Solvents

toluene THF

THF

THF

Conditions

Workup

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

Procedure

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:

Source