Tetrahydrofuran → HCID 68489914, compound

Temperature

0 °C

(2-Amino-5-chlorophenyl)(cyclopropyl)methanone (450 mg, 2.30 mmol) was dissolved in THF (5 mL), and while stirring the reaction solution at 0° C., vinyl magnesium bromide (1.0 M THF solution, 5.7 mL) was added dropwise thereto. The reaction solution was stirred overnight at room temperature, and then, a saturated aqueous ammonium chloride solution was added to the solution. After the solution was diluted with ethyl acetate, the organic layer was separated and washed with saturated brine and then dried over magnesium sulfate. After the drying agent was removed by filtration, the solvent was evaporated under reduced pressure. The resulting residue was dissolved in THF (5 mL), and 1,1-carbonyldiimidazole (CDI) (745 mg) was added thereto at room temperature. The reaction solution was stirred at room temperature for 2 hours, followed by ice-cooling, and water was added to the reaction solution. The solution was diluted with ethyl acetate and a saturated aqueous ammonium chloride solution was added thereto. The organic layer was separated and washed with saturated brine and then dried over magnesium sulfate. After the drying agent was removed by filtration, the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (ethyl acetate/hexane=1/2), whereby 6-chloro-4-cyclopropyl-4-vinyl-1,4-dihydro-2H-3,1-benzoxazin-2-one (610 mg) was quantitatively obtained as a pale white solid.

1. stirringThe reaction solution was stirred overnight at room temperature
2. customthe organic layer was separated
3. washwashed with saturated brine
4. dry with materialdried over magnesium sulfate
5. customAfter the drying agent was removed by filtration
6. customthe solvent was evaporated under reduced pressure
7. dissolutionThe resulting residue was dissolved in THF (5 mL)
8. addition1,1-carbonyldiimidazole (CDI) (745 mg) was added
9. customat room temperature
10. stirringThe reaction solution was stirred at room temperature for 2 hours
11. temperaturecooling
12. additionwater was added to the reaction solution
13. additionThe solution was diluted with ethyl acetate
14. additiona saturated aqueous ammonium chloride solution was added
15. customThe organic layer was separated
16. washwashed with saturated brine
17. dry with materialdried over magnesium sulfate
18. customAfter the drying agent was removed by filtration
19. customthe solvent was evaporated under reduced pressure
20. customThe resulting residue was purified by silica gel column chromatography (ethyl acetate/hexane=1/2), whereby 6-chloro-4-cyclopropyl-4-vinyl-1,4-dihydro-2H-3,1-benzoxazin-2-one (610 mg)
21. customwas quantitatively obtained as a pale white solid

ORD record

ord-0e1d2e43bc1f4cdabdbb11a1b9fc186b

Source dataset

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08314094B2