N-bromobutanimide → 2-Bromo-5-fluoro-4-nitroaniline

Temperature

22 °C

A flask was charged with 3-fluoro-4-nitroaniline (1.0 equiv) followed by ethyl acetate (10 vol) and stirred to dissolve all solids. N-Bromosuccinimide (1.0 equiv) was added as a portion-wise as to maintain internal temperature of 22° C. At the end of the reaction, the reaction mixture was concentrated in vacuo on a rotavap. The residue was slurried in distilled water (5 vol) to dissolve and remove succinimide. (The succinimide can also be removed by water workup procedure.) The water was decanted and the solid was slurried in 2-propanol (5 vol) overnight. The resulting slurry was filtered and the wetcake was washed with 2-propanol, dried in vacuum oven at 50° C. overnight with N2 bleed until constant weight was achieved. A yellowish tan solid was isolated (50% yield, 97.5% AUC). Other impurities were a bromo-regioisomer (1.4% AUC) and a di-bromo adduct (1.1% AUC). 1H NMR (500 MHz, DMSO) δ 8.19 (1H, d, J=8.1 Hz), 7.06 (br. s, 2H), 6.64 (d, 1H, J=14.3 Hz).

1. dissolutionto dissolve all solids
2. customAt the end of the reaction
3. concentrationthe reaction mixture was concentrated in vacuo on a rotavap
4. dissolutionto dissolve
5. customremove succinimide
6. custom(The succinimide can also be removed by water workup procedure
7. custom) The water was decanted
8. filtrationThe resulting slurry was filtered
9. washthe wetcake was washed with 2-propanol
10. dry with materialdried in vacuum oven at 50° C. overnight with N2
11. customA yellowish tan solid was isolated (50% yield, 97.5% AUC)

ORD record

ord-433c3a275c924db5a747e5307852bf4a

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09051303B2