Pyridine, hydrofluoride (1:1) → 2-Cyano-5-fluoropyridine

Temperature

65 °C

To a 100 mL round bottom flask charged with 5-aminopicolinonitrile (285 mg, 2.44 mmol) at 0° C. was added HF-pyridine (5 mL) under N2. A pale brown solution was formed. In 4 aliquots, NaNO2 (250 mg, 3.62 mmol) was added with stirring. The solution turned green and a brown gas was liberated. After 20 min at 0° C., the solution was allowed to reach rt and stirred for an additional 20 min. A reflux condenser was attached and the reaction mixture was heated at 65° C. for 20 min then allowed to cool to rt. The orange slurry was quenched by the addition of crushed ice and the aqueous layer was extracted with DCM (3×10 mL). The combined organic portions were dried over Na2SO4, decanted and concentrated under reduced pressure to yield 5-fluoropicolinonitrile (152 mg, 52% yield) as a pale orange powder. LCMS: RT=0.63 min [M+H] 122.9 (2 min Phenomenex Luna C18 column, 4.6×30 mm eluting with 10-90% MeOH/H2O over 2 minutes containing 0.1% TFA; 5 mL/min, monitoring at 220 nm); HPLC: RT=0.99 min (Phenomenex Luna C18 column, 4.6×50 mm eluting with 10-90% MeOH/H2O over 4 minutes containing 0.2% PPA; 4 mL/min, monitoring at 220 nm, Purity 96%); NMR: 400 MHz 1H (CDCl3) ppm 8.52 (d, J=2.64 Hz, 1H), 7.70 (dd, J=4.4 and J=8.36 Hz, 1H), 7.50 (m, 1 H).

1. customA pale brown solution was formed
2. customto reach rt
3. stirringstirred for an additional 20 min
4. customA reflux condenser was attached
5. temperatureto cool to rt
6. customThe orange slurry was quenched by the addition of crushed ice
7. extractionthe aqueous layer was extracted with DCM (3×10 mL)
8. dry with materialThe combined organic portions were dried over Na2SO4
9. customdecanted
10. concentrationconcentrated under reduced pressure

ORD record

ord-ac58142b852c4194b3cc5c6fe4744da3

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08404896B2