Carbon Dioxide → 3-Fluoropyridine-4-carboxylic acid

While a mixture of 3.54 g of diisopropylamine and 50 ml of tetrahydrofuran was cooled in a dry ice-acetone bath, 20 ml of 1.6 M hexane solution of n-butyllithium was added while stirring so that the temperature of the reaction mixture did not exceed −40° C. Thereafter, the reaction mixture was stirred for 30 minutes. Then, a mixture of 2.91 g of 3-fluoropyridine and 3 ml of tetrahydrofuran was added so that the temperature of the reaction mixture did not exceed −60° C. The mixture was further stirred for 30 minutes. After crushed dry ice was added to the reaction mixture, cooling was stopped. Then, the reaction mixture was stirred until the temperature returned to room temperature. Water was added to the reaction mixture, and most part of hexane and tetrahydrofuran was removed under reduced pressure. The residue was washed with tert-butyl methyl ether, and the aqueous layers were collected. To the collected aqueous layer, concentrated hydrochloric acid was added while ice-cooling, and pH of the mixture was made to be 3 and stirred for one hour. Precipitates were collected by filtration and dried under reduced pressure to give 3.59 g of 3-fluoroisonicotinic acid.

1. temperaturewas cooled in a dry ice-acetone bath
2. customdid not exceed −40° C
3. stirringThereafter, the reaction mixture was stirred for 30 minutes
4. additionwas added so that the temperature of the reaction mixture
5. customdid not exceed −60° C
6. stirringThe mixture was further stirred for 30 minutes
7. additionwas added to the reaction mixture
8. temperaturecooling
9. stirringThen, the reaction mixture was stirred until the temperature
10. customreturned to room temperature
11. customwas removed under reduced pressure
12. washThe residue was washed with tert-butyl methyl ether
13. customthe aqueous layers were collected
14. additionTo the collected aqueous layer, concentrated hydrochloric acid was added while ice-
15. temperaturecooling
16. stirringstirred for one hour
17. customPrecipitates
18. filtrationwere collected by filtration
19. customdried under reduced pressure

ORD record

ord-87cdfe90fe8b4c5295e22dd9f160f4d1

Source dataset

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08445522B2