Iodoethane → 3-Methylisonicotinonitrile

To a solution of 3-picoline N-oxide (60 g, 0.55 mol) in dichloromethane (1000 mL) was added ethyl iodide (132 mL, 1.65 mol) and the mixture stirred at room temperature for 16 hours. The precipitate was collected by filtration and washed with diethyl ether (200 mL) to give a white solid. The solid was dissolved in water (600 mL) and warmed to 50° C. Sodium cyanide (50 g, 1.02 mol) was added as a solution in water (180 mL) over 1 hour, keeping the internal temperature below 60° C. and the resulting dark brown solution was stirred at 55° C. for a further 1 hour. The reaction mixture was extracted with diethyl ether (3×600 mL). The combined organic extracts were dried (MgSO4) and concentrated under reduced pressure to give a brown oil. The crude product was purified by column chromatography on silica gel eluting with a solvent gradient of n-pentane:dichloromethane (40:60 to 0:100). The product was co-evaporated with dichloromethane (2×300 mL) to give the title compound as a colourless oil (30.5 g, 47%).

1. filtrationThe precipitate was collected by filtration
2. washwashed with diethyl ether (200 mL)
3. customto give a white solid
4. temperaturewarmed to 50° C
5. customthe internal temperature below 60° C.
6. stirringthe resulting dark brown solution was stirred at 55° C. for a further 1 hour
7. extractionThe reaction mixture was extracted with diethyl ether (3×600 mL)
8. dry with materialThe combined organic extracts were dried (MgSO4)
9. concentrationconcentrated under reduced pressure
10. customto give a brown oil
11. customThe crude product was purified by column chromatography on silica gel eluting with a solvent gradient of n-pentane:dichloromethane (40:60 to 0:100)

ORD record

ord-b38b87f4e9d244cf99e6b4999f9764d9

Source dataset

uspto-grants-2005_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06936619B2