Ethyl isonicotinate → HCID 18446612, compound

Participants

Reaction Conditions

Reaction Steps

To a cold (O ° C.) solution of 6-chloro-2-picoline (14.5 mL, 132.3 mmol) and ethyl isonicotinate (20.0 g, 132.3 mmol) in tetrahydrofuran (300 mL) was added lithium bis(trimethylsilyl)amide (280 mL 1.0 M in tetrahydrofuran, 278 mmol) dropwise via a pressure equalizing funnel over 1 hour. Upon complete addition, the cold bath was removed and the resulting solution was heated at 45° C. for 15 hours. The mixture was cooled to room temperature, methanol was added, and the solution was concentrated to give 2-(6-chloro-2-pyridinyl)-1-(4-pyridinyl)ethanone as a syrup, that was used without further purification. This syrup (11.7 g, 50 mmol) was dissolved in methanol (200 mL). To this solution was added hydroxylamine hydrochloride (17.5 g, 250 mmol) followed by the addition of a sodium hydroxide solution (10 g, 250 mmol in 30 mL of water). The resulting suspension was heated at reflux for 2 hours and then allowed to cool to room temperature. The mixture was concentrated and water was added to the resulting slurry. A white precipitate formed, which was collected by filtration, washed with water and dried to give 2-(6-chloro-2-pyridinyl)-1-(4-pyridinyl)ethanone oxime (10.5 g, 850%) as a white solid. 1H NMR (CDCl3): δ 9.6 (broad s, 1H), 8.65 (d, 2H), 7.70 (d, 2H), 7.58 (t, 1H), 7.22 (m, 2H), 4.40 (s, 2H); MS m/248 (M+1).

Provenance & Evidence