1-Chloroethyl chloroformate → 1,1-Diphenyltetrahydro-1H-oxazolo[3,4-a]pyrazin-3(5H)-one

Temperature

60 °C

To a solution of hexahydro-1,1-diphenyl-7-(phenylmethyl)-3H-oxazolo[3,4-a]pyrazin-3-one (19 g, 48 mmol) in 1,2-dichloroethane (80 mL) was added 1-chloroethyl chloroformate (8.7 g, 61 mmol), and the mixture was stirred at 60° C. for 3 hours. 1-Chloroethyl chloroformate (1.7 g, 12 mmol) was further added thereto, and the resulting mixture was stirred at 60° C. for 2 hours. The reaction solution was concentrated under reduced pressure and methanol was added thereto, and the mixture was heated under reflux for 2.5 hours. The reaction solution was concentrated under reduced pressure, and crystallized by adding ethyl acetate and hexane. The precipitated crystals were collected by filtration. The crystals were dissolved by adding ethyl acetate and an aqueous saturated sodium hydrogen carbonate solution. Then, the organic layer was washed with water and concentrated under reduced pressure. To the residue was added diisopropyl ether, and the precipitated crystals were washed with diisopropyl ether and dried to obtain the title compound (13 g, yield 92%). 1H NMR of the above obtained compound corresponded with the compound obtained in Reference Example 2.

1. stirringthe resulting mixture was stirred at 60° C. for 2 hours
2. concentrationThe reaction solution was concentrated under reduced pressure and methanol
3. additionwas added
4. temperaturethe mixture was heated
5. temperatureunder reflux for 2.5 hours
6. concentrationThe reaction solution was concentrated under reduced pressure
7. customcrystallized
8. additionby adding ethyl acetate and hexane
9. filtrationThe precipitated crystals were collected by filtration
10. dissolutionThe crystals were dissolved
11. additionby adding ethyl acetate
12. washThen, the organic layer was washed with water
13. concentrationconcentrated under reduced pressure
14. additionTo the residue was added diisopropyl ether
15. washthe precipitated crystals were washed with diisopropyl ether
16. customdried

ORD record

ord-8dbc3bf49c4245b4b2d5557360e8fffd

Source dataset

uspto-grants-2010_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07795267B2