Carbon Dioxide → 2,6-Difluoropyridine-3-carboxylic acid

Temperature

5 °C

Fifty (50) g of 2,6-difluoropyridine was dissolved in 200 ml of tetrahydrofuran, and into the solution 326 ml of 1.6M n-butyl lithium-tetrahydrofuran solution was added dropwise at -70° C., followed by an hour's stirring at the same temperature. To the reaction mixture 29 g of dry ice blocks were added little by little, followed by 30 minutes' stirring at the same temperature. Raising the temperature to about 5° C., 500 ml of ice water was added. The reaction mixture was washed twice with ethyl acetate, and the aqueous layer was adjusted to pH 3 with conc. hydrochloric acid. The aqueous layer was then extracted with chloroform. The extract was washed with saturated saline water, dried over anhydrous magnesium sulfate, and the solvent was concentrated under reduced pressure. The crystalline precipitate was collected by filtration, and recrystallized from diethyl ether-n-hexane to provide 63 g of 2,6-difluoro-3-pyridinecarboxylic acid (m.p. 170-171° C.).

1. waitfollowed by an hour
2. stirring' stirring at the same temperature
3. washThe reaction mixture was washed twice with ethyl acetate
4. extractionThe aqueous layer was then extracted with chloroform
5. washThe extract was washed with saturated saline water
6. dry with materialdried over anhydrous magnesium sulfate
7. concentrationthe solvent was concentrated under reduced pressure
8. filtrationThe crystalline precipitate was collected by filtration
9. customrecrystallized from diethyl ether-n-hexane

ORD record

ord-daea3517f5a44d9cbe7ecab04e148618

Source dataset

uspto-grants-1999_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05945415