Dichloromethane → 2-Chloro-5-fluoropyridine-3-carbonitrile

Temperature

0 °C

To an oven-dried, 250 mL, round-bottomed flask were added the crude 2-chloro-5-fluoronicotinamide (1.05 g, 6.00 mmol) from above, anhydrous dichloromethane (25 mL), and triethylamine (2.12 g, 2.92 mL, 21.0 mmol). The flask was sealed with a septum and cooled to 0° C. in an ice bath. Neat trifluoroacetic anhydride (1.89 g, 1.25 mL, 9.00 mmol) was added slowly via syringe and the resulting solution was stirred at 0° C. for 30 minutes then allowed to warm to room temperature over 1 hour. Water (20 mL) was added, and the mixture was transferred to a separatory funnel. The mixture was extracted with dichloromethane (3×20 mL). The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated by rotary evaporator to give a golden oil. The product was purified by flash chromatography (silica gel: 10% ethyl acetate, 90% hexanes—product Rf˜0.3) to give 862 mg (92%) of the title compound as a pale yellow solid. 1H NMR (CDCl3) δ 8.66 (dd, J=7.8, 3.0 Hz, 1H), 8.82 (d, J=2.7 Hz, 1H).

1. customThe flask was sealed with a septum
2. temperatureto warm to room temperature over 1 hour
3. customthe mixture was transferred to a separatory funnel
4. extractionThe mixture was extracted with dichloromethane (3×20 mL)
5. dry with materialThe combined organic extracts were dried over magnesium sulfate
6. filtrationfiltered
7. concentrationconcentrated by rotary evaporator
8. customto give a golden oil
9. customThe product was purified by flash chromatography (silica gel: 10% ethyl acetate, 90% hexanes—product Rf˜0.3)

ORD record

ord-87f06657f4694a08b85de9eb8a574039

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08546374B2