Nitric Acid → 2,3,6-Trifluoro-5-nitropyridine

Temperature

60 °C

To a 3-neck, round-bottomed flask was added 2,3,6-trifluoropyridine (25 g, 0.19 mol) followed by the addition of red fuming nitric acid (210 mL, 4.7 mol). Sulfuric acid (150 mL, 2.8 mol) was added to this mixture slowly via an addition funnel, maintaining internal temperature below 40° C. The resulting solution was heated to 60° C. for 30 minutes and allowed to cool to room temperature after heating. This solution was then further cooled in an ice-water bath and inversely quenched into a 2-L Erlenmeyer flask containing a mixture of ice and water (700 mL, 1:1 ratio). The quenched solution was then transferred to a 2-L separatory funnel and partitioned with hexanes (600 mL). The aqueous layer was subsequently washed with hexanes (600 mL) and methylene chloride (600 mL). The combined organic layers were then dried over Na2SO4, filtered, and concentrated to provide the title compound as a light yellow liquid (19.2 g, 57% yield).

1. temperaturemaintaining internal temperature below 40° C
2. temperatureto cool to room temperature
3. temperatureafter heating
4. temperatureThis solution was then further cooled in an ice-water bath
5. custominversely quenched into a 2-L Erlenmeyer flask
6. additioncontaining
7. additiona mixture of ice and water (700 mL, 1:1 ratio)
8. customThe quenched solution was then transferred to a 2-L separatory funnel
9. custompartitioned with hexanes (600 mL)
10. washThe aqueous layer was subsequently washed with hexanes (600 mL) and methylene chloride (600 mL)
11. dry with materialThe combined organic layers were then dried over Na2SO4
12. filtrationfiltered
13. concentrationconcentrated

ORD record

ord-957ca567874e44b1bec3aff8701268fe

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08486966B2