Sodium hydride → tert-butyl 3-oxotetrahydro-1H-oxazolo[3,4-a]pyrazine-7(3H)-carboxylate

Temperatur

50 °C

1,4-Di(tert-butoxycarbonyl)piperazine-2-carboxylic acid (14.45 g, 43.7 mmol) was dissolved in THF (200 mL), and borane-THF complex (1.0 M solution in THF, 100 mL, 100 mmol) was added slowly. Upon complete addition, the reaction mixture was heated to 50° C. After 2 h, the reaction mixture was allowed to cool to rt and was slowly quenched by the dropwise addition of MeOH (50 mL). After gas evolution ceased, the reaction mixture was heated to 50° C. for 1 h. Upon cooling to rt, the reaction mixture was concentrated under reduced pressure. The material was dissolved in THF (200 mL) and NaH (60% dispersion in mineral oil, 1.75 g, 43.7 mmol) was added portion wise. The reaction mixture was heated to 50° C. overnight. Upon cooling to rt, the reaction mixture was quenched with H2O (300 mL) and extracted with EtOAc (3×400 mL). The combined organics were dried over Na2SO4, filtered, and concentrated under reduced pressure. The material was purified by column chromatography (10 to 40% EtOAc in Hexanes gradient) to give 6.31 g (59%) of the desired product as a white solid. Rf=0.43 in 80% EtOAc in Hexanes. 1.10 g (8%) of di-tert-butyl 2-(hydroxymethyl)piperazine-1,4-dicarboxylate was also isolated. Rf=0.63 in 80% EtOAc in Hexanes.

1. additionUpon complete addition
2. temperatureto cool to rt
3. customwas slowly quenched by the dropwise addition of MeOH (50 mL)
4. temperaturethe reaction mixture was heated to 50° C. for 1 h
5. temperatureUpon cooling to rt
6. concentrationthe reaction mixture was concentrated under reduced pressure
7. dissolutionThe material was dissolved in THF (200 mL)
8. temperatureThe reaction mixture was heated to 50° C. overnight
9. temperatureUpon cooling to rt
10. customthe reaction mixture was quenched with H2O (300 mL)
11. extractionextracted with EtOAc (3×400 mL)
12. dry with materialThe combined organics were dried over Na2SO4
13. filtrationfiltered
14. concentrationconcentrated under reduced pressure
15. customThe material was purified by column chromatography (10 to 40% EtOAc in Hexanes gradient)

ORD-Eintrag

ord-f4617b5067504fd1b21da4330044af6a

Quelldatensatz

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08822472B2