Dimethylformamide → 2-(Trifluoromethyl)pyridine-3-carbonitrile

Temperature

120 °C

To an oven-dried, N2-purged, 100-mL, round-bottomed flask containing a magnetic stir bar were added copper(I) iodide (1.26 g, 6.6 mmol) and potassium fluoride (383 mg, 6.6 mmol). The flask was heated to 120° C. for 1 hour under vacuum. After cooling to room temperature, 2-iodonicotinonitrile (1.38 g, 6.00 mmol) was added followed by the addition via syringe of anhydrous dimethylformamide (6 mL) and anhydrous N-methylpyrrolidinone (6 mL). A solution of (trifluoromethyl)trimethylsilane (12 mL of 0.5 M, 6.00 mmol) in tetrahydrofuran was added via syringe and the reaction mixture was stirred at room temperature overnight. Water (20 mL) was added. The mixture was transferred to a separatory funnel and extracted with ether (3×30 mL). The combined organic extracts were washed with ammonium hydroxide (30 mL), 1N hydrochloric acid (30 mL), and saturated sodium bicarbonate (30 mL). The ether solution was dried over magnesium sulfate and concentrated by rotary evaporator. The product was purified by flash chromatography (silica gel: 35% ethyl acetate, 65% hexanes, product Rf˜0.3) to give 800 mg (77%) of the title compound as a white powder. 1H NMR (CDCl3) δ 7.69 (dd, J=8.0, 4.9 Hz, 1H), 8.21 (dd, J=8.0, 1.5 HZ, 1H), 8.92 (dd, J=4.7, 9.4 Hz, 1H).

1. customTo an oven-dried, N2-purged
2. addition100-mL, round-bottomed flask containing a magnetic stir bar
3. temperatureAfter cooling to room temperature
4. customThe mixture was transferred to a separatory funnel
5. extractionextracted with ether (3×30 mL)
6. washThe combined organic extracts were washed with ammonium hydroxide (30 mL), 1N hydrochloric acid (30 mL), and saturated sodium bicarbonate (30 mL)
7. dry with materialThe ether solution was dried over magnesium sulfate
8. concentrationconcentrated by rotary evaporator
9. customThe product was purified by flash chromatography (silica gel: 35% ethyl acetate, 65% hexanes, product Rf˜0.3)

ORD record

ord-7e531b921b0b4b018b00976ea55649a0

Source dataset

uspto-grants-2012_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08217067B2