(Diethylamino)sulfur trifluoride → 2-Chloro-4-(1-fluoroethyl)pyridine

Temperature

-78 °C

1-(2-Chloropyridin-4-yl)ethan-1-ol (115 g, 729 mmol, 1.00 equiv) and dichloromethane (3300 mL) were added to a 5000-mL 4-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen. DAST (144 g, 893 mmol, 1.25 equiv) was added dropwise with stirring at −78° C. in 30 min. The resulting solution was stirred overnight at room temperature. The reaction was then slowly quenched by the addition of water (1000 mL). The resulting solution was extracted with dichloromethane (3×1000 mL). The combined organic layer was washed with brine (3×1000 mL), dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified by column chromatography on silica gel column (1:10 ethyl acetate/petroleum ether) to afford 2-chloro-4-(1-fluoroethyl)pyridine as light yellow oil.

1. custompurged
2. temperaturemaintained with an inert atmosphere of nitrogen
3. stirringThe resulting solution was stirred overnight at room temperature
4. customThe reaction was then slowly quenched by the addition of water (1000 mL)
5. extractionThe resulting solution was extracted with dichloromethane (3×1000 mL)
6. washThe combined organic layer was washed with brine (3×1000 mL)
7. dry with materialdried over anhydrous sodium sulfate
8. concentrationconcentrated under vacuum
9. customThe residue was purified by column chromatography on silica gel column (1:10 ethyl acetate/petroleum ether)

ORD record

ord-fbb7b85e464e4b73bceee8a4749619f3

Source dataset

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09242984B2