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

Temperatur

145 °C

A 5 N sodium hydroxide aqueous solution (450 mL), water (1000 mL), and 50% toluene-THF (2000 mL) were added to (S)-1-[(S)-1-(2,6-difluoropyridin-3-yl)ethylamino]propan-2-ol (+)-di-p-toluoyl-D-tartrate (199 g). The organic layer was separated. The water layer was extracted with 50% toluene-THF (800 mL) three times. All the organic layers were combined and concentrated under reduced pressure. To the residue, diethyl oxalate (200 mL) was added. The resulting reaction solution was heated to and stirred at 140 to 150° C. After 3 hr, the reaction solution was diluted with toluene (500 mL) and cooled with ice while stirring. The precipitated crystal was filtered, washed with toluene and diethyl ether, and dried in air to give 103 g of the title compound. The physical property values of this compound were as follows:

1. customThe organic layer was separated
2. extractionThe water layer was extracted with 50% toluene-THF (800 mL) three times
3. concentrationconcentrated under reduced pressure
4. additionTo the residue, diethyl oxalate (200 mL) was added
5. customThe resulting reaction solution
6. temperaturewas heated to and
7. temperaturecooled with ice
8. stirringwhile stirring
9. filtrationThe precipitated crystal was filtered
10. washwashed with toluene and diethyl ether
11. customdried in air

ORD-Eintrag

ord-7cdbe5d8d81b47a0bfbbe574f17b9e82

Quelldatensatz

uspto-grants-2010_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07737141B2