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

Temperature

-78 °C

A solution of n-butyl lithium in THF (2.62 M, 29.1 mL) was added dropwise to a solution of diisopropylamine (11.7 mL) in tetrahydrofuran (310 mL) under ice-cooling in a nitrogen atmosphere. The reaction solution was stirred under ice-cooling for one hour and then cooled to −78° C. A solution of 2,6-difluoropyridine (8 g) in tetrahydrofuran (10 mL) was added dropwise to the reaction solution. The reaction solution was stirred at −0.78° C. for three hours. Then, an excess amount of crushed dry ice was added in a nitrogen stream, and the reaction solution was stirred at −78° C. for 20 minutes and at room temperature for three hours. Water and diethyl ether were added to the reaction solution, and the aqueous layer was separated. The aqueous layer was adjusted to pH 1 by concentrated hydrochloric acid. Ethyl acetate was added to the aqueous layer, and the organic layer was separated. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure to obtain 10.4 g of the title compound.

1. temperaturecooling in a nitrogen atmosphere
2. temperaturecooling for one hour
3. stirringThe reaction solution was stirred at −0.78° C. for three hours
4. stirringthe reaction solution was stirred at −78° C. for 20 minutes and at room temperature for three hours
5. customthe aqueous layer was separated
6. additionEthyl acetate was added to the aqueous layer
7. customthe organic layer was separated
8. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
9. customthe solvent was evaporated under reduced pressure

ORD record

ord-28508767ac704a6cb7eeef4f5e401359

Source dataset

uspto-grants-2009_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07618960B2