Nitric Acid → 2-Hydroxy-5-nitro-3-(trifluoromethyl)pyridine

Temperature

90 °C

A mixture of 3-(trifluoromethyl)pyridin-2(1H)-one 2 (2.00 g, 12.26 mmol) and sulfuric acid (H2SO4, 3.5 ml, 30%) was heated to 90° C. and nitric acid (HNO3, 2.5 ml, 65%) was added. The mixture was stirred at 90° C. for 8 hours and additional nitric acid (1 ml, 65%) was added. The mixture was stirred for an additional 6 hours at 90° C. and was then poured into a beaker containing ice (30 ml). The mixture was diluted with water (30 ml) and 6N aqueous NaOH was added until a pH of about 4 to about 5. The mixture was extracted with ethyl acetate (3×40 ml), the combined organic phases dried over Na2SO4 and all solvents were removed under reduced pressure. The residue was dissolved in ethyl acetate and the product precipitated by the addition of hexane. After filtration, 5-nitro-3-(trifluoromethyl)pyridin-2(1H)-one 3 was obtained as a yellow powder (1.58 g, 7.59 mmol, 62%).

1. stirringThe mixture was stirred for an additional 6 hours at 90° C.
2. additionwas then poured into a beaker
3. additionwas added until a pH of about 4 to about 5
4. extractionThe mixture was extracted with ethyl acetate (3×40 ml)
5. dry with materialthe combined organic phases dried over Na2SO4
6. customall solvents were removed under reduced pressure
7. dissolutionThe residue was dissolved in ethyl acetate
8. customthe product precipitated by the addition of hexane
9. filtrationAfter filtration

ORD record

ord-97fa53496b524781bab56d4654519d98

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08802689B2