N-bromobutanimide → 4-Bromo-3-chloro-5-fluoroaniline

Temperature

0 °C

3-Chloro-5-fluoroaniline (2061 mmol, 300 g) was dissolved in ACN (3000 ml) and the solution cooled to 0° C. NBS (2061 mmol, 367 g) was added to the reaction mixture in small portions keeping the temperature below 10° C. Reaction mixture was stirred at 10±5° C. for 3.5 h. 10% Aqueous NaHSO3 was added and the reaction mixture was concentrated under vacuum to remove organic solvents. Water and DCM was added, stirred for 15 min and the phases were separated. The water phase was extracted with DCM. The combined organics were washed with water. The organic phase was evaporated. 2-Propanol was added to the residue and distilled until the steam temperature was 80° C. Water was added and the temperature was kept at 40±10° C. The mixture was cooled to 5° C. and stirred for 4 h. The precipitate was removed by filtration, washed with water and dried under vacuum. 440.7 g of the title compound was obtained. 1H-NMR (400 MHz, DMSO-d6): δ 5.87 (s, 2H), 6.42-6.49 (m, 1H), 6.62-6.66 (m, 1H).

1. customthe temperature below 10° C
2. customReaction mixture
3. concentrationthe reaction mixture was concentrated under vacuum
4. customto remove organic solvents
5. additionWater and DCM was added
6. stirringstirred for 15 min
7. customthe phases were separated
8. extractionThe water phase was extracted with DCM
9. washThe combined organics were washed with water
10. customThe organic phase was evaporated
11. addition2-Propanol was added to the residue
12. distillationdistilled until the steam temperature
13. customwas 80° C
14. additionWater was added
15. customwas kept at 40±10° C
16. temperatureThe mixture was cooled to 5° C.
17. stirringstirred for 4 h
18. customThe precipitate was removed by filtration
19. washwashed with water
20. customdried under vacuum

ORD record

ord-8ad8e8d354194f398b6d6e36dd4f41c0

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08921378B2