5-Bromouracil → Urea, (2,6-difluorobenzyl)-

Temperature

80 °C

A suspension of 5-bromouracil (18.45 g, 96.6 mmol) in 300 mL of dichloroethane was treated with N,O-bis(trimethylsilyl)acetamide (48 mL, 39.5 g, 194 mmol). The reaction mixture was heated at 80° C. for 3 hr under the nitrogen. The solution was cooled down to ambient temperature, 2,6-difluorobenzyl bromide (25 g, 120 mmol) was added and the reaction mixture was heated at 80° C. overnight under the protection of nitrogen. The reaction was cooled down, quenched with MeOH (15 mL), and partitioned between dichloromethane (500 mL) and water (250 mL). The organic layer was washed with brine, dried (sodium sulfate), and evaporated to give a solid. The crude product was triturated with ether, filtered, and washed with ether three times to give compound 1 (15.2 g, 50%) as a white solid; MS (CI) m/z 316.90, 318.90 (MH+).

1. temperatureThe solution was cooled down to ambient temperature
2. temperaturethe reaction mixture was heated at 80° C. overnight under the protection of nitrogen
3. temperatureThe reaction was cooled down
4. customquenched with MeOH (15 mL)
5. custompartitioned between dichloromethane (500 mL) and water (250 mL)
6. washThe organic layer was washed with brine
7. dry with materialdried (sodium sulfate)
8. customevaporated
9. customto give a solid
10. customThe crude product was triturated with ether
11. filtrationfiltered
12. washwashed with ether three times

ORD record

ord-a3597a87fcc54dd7aa65f2a5ad3fd52d

Source dataset

uspto-grants-2003_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06608197B2