Triethylamine → 6-bromo-1-(4-methoxybenzyl)-4-(trifluoromethyl)-4-vinyl-1,4-dihydro-2H-3,1-benzoxazin-2-one

Temperature

0 °C

To a stirred solution of 1-{5-bromo-2-[(4-methoxybenzyl)amino]phenyl}-2,2,2-trifluoroethanone (75.5 g, 0.195 mol) in THF (500 mL), vinyl magnesium bromide (1.0 M THF solution, 389 mL) was added dropwise at 0° C. over 1 hour. After the reaction solution was stirred at 0° C. for 3 hours, a saturated aqueous ammonium chloride solution (100 mL) was added thereto, and the solution was further stirred at room temperature for 10 minutes. The reaction solution was diluted with ethyl acetate and the organic layer was separated. The organic layer was washed with water and saturated brine and then dried over magnesium sulfate. After the drying agent was removed by filtration, the solvent was evaporated under reduced pressure. The residue was dissolved in triethylamine (81.2 mL, 0.59 mol) and toluene (500 mL), and while stirring the resulting solution, triphosgene (57.9 g, 0.195 mol) was gradually added thereto at 0° C. After the reaction solution was stirred at 0° C. for 30 minutes, a saturated aqueous sodium hydrogen carbonate solution (100 mL) was added thereto, and the solution was further stirred at 0° C. for 10 minutes. The reaction solution was diluted with ethyl acetate and the organic layer was separated. The organic layer was washed with water and saturated brine and then dried over magnesium sulfate. After the drying agent was removed by filtration, the solvent was evaporated under reduced pressure. The residue was suspended in hexane (50 mL) and the suspension was stirred overnight at room temperature. The resulting solid was collected by filtration and washed with hexane and then dried, whereby the objective compound (71.6 g, 83%) was obtained as a pale yellow solid.

1. stirringthe solution was further stirred at room temperature for 10 minutes
2. customthe organic layer was separated
3. washThe organic layer was washed with water and 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. additionwas gradually added
8. customat 0° C
9. stirringAfter the reaction solution was stirred at 0° C. for 30 minutes
10. stirringthe solution was further stirred at 0° C. for 10 minutes
11. customthe organic layer was separated
12. washThe organic layer was washed with water and saturated brine
13. dry with materialdried over magnesium sulfate
14. customAfter the drying agent was removed by filtration
15. customthe solvent was evaporated under reduced pressure
16. stirringthe suspension was stirred overnight at room temperature
17. filtrationThe resulting solid was collected by filtration
18. washwashed with hexane
19. customdried

ORD record

ord-283256424f8640c58347529fc8ccebcb

Source dataset

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08314094B2