Dimethylformamide → 4-Chloro-5-fluoropyridine-3-carbaldehyde

Temperature

-78 °C

To a solution of diisopropylamine (6.4 mL, 45.6 mmol) in THF (50 mL) at −30° C. was added n-butyllithium (2.5 M in hexanes, 18.2 mL, 45.6 mmol) over 15 minutes and the resulting mixture stirred for 15 minutes then cooled to −78° C. A solution of 4-chloro-3-fluoro-pyridine (5.0 g, 38.0 mmol) in THF (10 mL) was added dropwise over 15 minutes then the resulting mixture was stirred at −78° C. for 18 hours. DMF (3.5 mL, 45.6 mmol) was added and the reaction was warmed to room temperature. The mixture was quenched with ammonium chloride (sat. aq., 300 mL) and extracted with ethyl acetate (3×100 mL). The combined organic extracts were dried over anhydrous sodium sulfate and concentrated to dryness under reduced pressure. The residue was purified by silica gel flash chromatography (0-40% ethyl acetate in cyclohexane) to afford the title compound as a pale orange solid (5.1 g, 84% yield). 1H NMR (300 MHz, CDCl3): δ 10.47 (s, 1H), 8.88 (s, 1H), 8.70 (s, 1H).

1. stirringthe resulting mixture was stirred at −78° C. for 18 hours
2. temperaturethe reaction was warmed to room temperature
3. customThe mixture was quenched with ammonium chloride (sat. aq., 300 mL)
4. extractionextracted with ethyl acetate (3×100 mL)
5. dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
6. concentrationconcentrated to dryness under reduced pressure
7. customThe residue was purified by silica gel flash chromatography (0-40% ethyl acetate in cyclohexane)

ORD record

ord-1a1cdc81dfb0461388ef69ca909f0b17

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09309240B2