Nitric Acid → 6-Fluoro-2-methyl-3-nitrobenzoic acid

Temperature

-2.5 °C

A solution of 2-fluoro-6-methylbenzoic acid (2 g, 12.98 mmol) in concentrated H2SO4 (15.77 ml, 295.85 mmol) was cooled to −5° C. in an acetone/ice bath in air. A mixture of concentrated nitric acid (1.08 ml, 16.87 mmol) and concentrated H2SO4 (1 ml, 18.76 mmol) was added dropwise to the reaction mixture at −5 to 0° C. over 15 minutes. The pale yellow reaction mixture was stirred at −5 to 0° C. for 30 minutes before being poured onto ice (100 g). The resulting precipitate was filtered and dissolved in EtOAc (50 ml) and the organic phase was washed with deionized water (25 ml) followed by brine (25 ml). The organic phase was dried over MgSO4, filtered and concentrated under reduced pressure to give 2 g (77%) of 6-fluoro-2-methyl-3-nitrobenzoic acid as a white solid. LC-MS 99%, 1.31 min (3 minute LC-MS method), m/z=198.0, 1H NMR (500 MHz, Chloroform-d) δ ppm 8.04 (dd, J=9.1, 5.0 Hz, 1H), 7.16 (t, J=8.6 Hz, 1H), 2.63 (s, 3H).

1. additionwas added dropwise to the reaction mixture at −5 to 0° C. over 15 minutes
2. additionbefore being poured onto ice (100 g)
3. filtrationThe resulting precipitate was filtered
4. dissolutiondissolved in EtOAc (50 ml)
5. washthe organic phase was washed with deionized water (25 ml)
6. dry with materialThe organic phase was dried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure

ORD record

ord-bcb93481b24c4ec390202d49cbe2c403

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08765732B2