Dimethylformamide → 6-Fluoropyridine-2-carboxaldehyde

Temperature

-78 °C

To a solution of diisopropylamine (6.54 mL, 1.2 equiv) in 30 mL of THF at 0° C., a solution of n-butyllithium (17.1 mL, 2.5M in hexanes) is added dropwise. Stirring is continued for 15 minutes at 0° C., the reaction is then cooled to −78° C. 2-Fluoro-6-methylpyridine (4.00 mL, 38.9 mmol) is added dropwise to the cold solution. The reaction mixture is stirred at −78° C. for 1 hours and then quenched with DMF (4.52 mL, 1.5 equiv). The reaction is maintained at −78° C. for 30 minutes and then warmed to 0° C. The cold solution is added to a mixture of sodium periodate (24.9 g) in 120 mL of water at 0° C. The reaction mixture is allowed to gradually warm to room temperature over 1 hours and then stirred at room temperature for 24 hours. The reaction mixture is filtered through a plug of celite to remove the precipitate and the plug is washed with ether. The organic layer is separated, washed with aqueous sodium bicarbonate (1×40 mL), then with 0.25M KH2PO4 (1×40 mL) and then brine (1×40 mL). The organic solution is dried (NaSO4) and concentrated in vacuo.

1. stirringThe reaction mixture is stirred at −78° C. for 1 hours
2. temperatureThe reaction is maintained at −78° C. for 30 minutes
3. temperaturewarmed to 0° C
4. temperatureto gradually warm to room temperature over 1 hours
5. stirringstirred at room temperature for 24 hours
6. filtrationThe reaction mixture is filtered through a plug of celite
7. customto remove the precipitate
8. washthe plug is washed with ether
9. customThe organic layer is separated
10. washwashed with aqueous sodium bicarbonate (1×40 mL)
11. dry with materialThe organic solution is dried (NaSO4)
12. concentrationconcentrated in vacuo

ORD record

ord-d196bd5bdc0845839c34c6a497440865

Source dataset

uspto-grants-2006_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06982268B2