Benzyl chloroformate → phenylmethyl (9aR)-octahydro-2H-pyrido[1,2-a]pyrazine-2-carboxylate

Temperatur

0 °C

(9aR)-Tetrahydro-2H-pyrido[1,2-a]pyrazine-1,4(3H,6H)-dione (779 mg, 4.63 mmol) was dissolved in 46 mL of THF and cooled to 0° C. LiAlH4 (352 mg, 9.57 mmol) was then added portion wise. The mixture was heated to 85° C. for 2 hours, then cooled to 0° C. The reaction was quenched with sodium sulphate decahydrate (704 mg, 9.27 mmol) and was stirred at 0° C. for 30 min. To this solution was added 1N aq. NaOH (5 mL) and the reaction mixture was stirred at 0° C. for 30 min. Then Et2O (20 mL) was added, followed by benzyl chloroformate (0.783 mL, 5.563 mmol). The reaction mixture was stirred vigorously at 0° C. for 2 h, the phases were separated, and the aqueous phase was extracted with Et2O (3×50 mL). The combined organic phase was dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The resulting crude product was purified by RP-HPLC to provide phenylmethyl (9aR)-octahydro-2H-pyrido[1,2-a]pyrazine-2-carboxylate (688 mg, 55%). LCMS: (M+H)+: 275.1.

1. temperatureThe mixture was heated to 85° C. for 2 hours
2. temperaturecooled to 0° C
3. stirringthe reaction mixture was stirred at 0° C. for 30 min
4. stirringThe reaction mixture was stirred vigorously at 0° C. for 2 h
5. customthe phases were separated
6. extractionthe aqueous phase was extracted with Et2O (3×50 mL)
7. dry with materialThe combined organic phase was dried over anhydrous MgSO4
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customThe resulting crude product was purified by RP-HPLC

ORD-Eintrag

ord-6b8df41468b44cedbbbbf4e97e262770

Quelldatensatz

uspto-grants-2011_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07893056B2