Hydrogen Bromide → 4-Bromo-5-fluoro-2-nitrotoluene

Temperature

0 °C

2-Fluoro-4-methyl-5-nitro-aniline (1.85 g, 10.90 mmol) was suspended in concentrated hydrobromic acid (22 mL) and cooled to 0° C. Solution of sodium nitrite (0.83 g, 12.00 mmol) in water (3.6 mL) was added dropwise while maintaining the temperature at 0˜5° C. After stirring for 15 min, the mixture was filtered through a cotton pad and slowly poured into a solution of cuprous oxide (2.60 g, 17.5 mmol) and concentrated hydrobromic acid (20 mL) at 0° C. After stirring overnight, the reaction mixture was diluted with EtOAc, washed with 10% aq NaOH and 5% aq Na2S2O5 successively, dried over MgSO4, filtered and concentrated. The residue was purified by column chromatography (ethyl acetate:hexane; 2:98) to afford 1-Bromo-2-fluoro-4-methyl-5-nitro-benzene as a colorless oil (2.30 g, 91%). 1H NMR (CDCl3, 400 MHz,): 2.59 (s, 3H), 7.11 (d, J=8.4 Hz, 1H), 8.24 (d, J=6.3 Hz, 1H).

1. temperaturewhile maintaining the temperature at 0˜5° C
2. filtrationthe mixture was filtered through a cotton pad
3. stirringAfter stirring overnight
4. washwashed with 10% aq NaOH and 5% aq Na2S2O5 successively
5. dry with materialdried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated
8. customThe residue was purified by column chromatography (ethyl acetate:hexane; 2:98)

ORD record

ord-ff3cbe6716aa49d7a64a0081db7502d5

Source dataset

uspto-grants-2012_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08207216B2