Potassium Carbonate → benzyl tetrahydro-3-oxo-1H-oxazolo[3,4-a]pyrazine-7(3H)-carboxylate

Temperatur

50 °C

1,4-Di((benzyloxy)carbonyl)piperazine-2-carboxylic acid (18.9 g, 47.4 mmol) was dissolved in THF (200 mL), and borane-THF complex (1.0 M solution in THF, 100 mL, 100 mmol) was added over about 15 min. Upon complete addition, the reaction mixture was heated to 50° C. After 3 h, the reaction mixture was allowed to cool to rt and was slowly quenched by the dropwise addition of MeOH. 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 EtOH (200 mL) and K2CO3 (6.9 g, 49.9 mmol) was added. The reaction mixture was heated to 70° C. overnight. Upon cooling to rt, the reaction mixture was concentrated under reduced pressure, diluted with H2O (200 mL) and extracted with EtOAc (3×200 mL). The combined organics were dried over Na2SO4, filtered, and concentrated under reduced pressure. The material was purified by column chomatography (10 to 40% EtOAc in Hexanes gradient) to give 10.26 g (78%) of the desired product as a white solid. An additional 0.452 g (3%) of the desired product was isolated from impure chomatography fractions by recrystallization from methyl tert-butyl ether. LC-MS: RT=7.848 min; [M+Na]+=299.1.

1. additionUpon complete addition
2. temperatureto cool to rt
3. customwas slowly quenched by the dropwise addition of MeOH
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 EtOH (200 mL)
8. temperatureThe reaction mixture was heated to 70° C. overnight
9. temperatureUpon cooling to rt
10. concentrationthe reaction mixture was concentrated under reduced pressure
11. additiondiluted with H2O (200 mL)
12. extractionextracted with EtOAc (3×200 mL)
13. dry with materialThe combined organics were dried over Na2SO4
14. filtrationfiltered
15. concentrationconcentrated under reduced pressure
16. customThe material was purified by column chomatography (10 to 40% EtOAc in Hexanes gradient)

ORD-Eintrag

ord-875f27a3aa344de18ca4e28c1da1863f

Quelldatensatz

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08822472B2