Ethyl isonicotinate → HCID 18446612, compound

Temperature

45 °C

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).

1. customover 1 hour
2. additionUpon complete addition
3. customthe cold bath was removed
4. temperatureThe mixture was cooled to room temperature
5. additionmethanol was added
6. concentrationthe solution was concentrated

ORD record

ord-e82b81fe2cd0489ba55520a08c318dee

Source dataset

uspto-grants-2007_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07199120B2