Carbon Dioxide → 3-Fluoropyridine-4-carboxylic acid

To a mixture of 39.9 ml of diisopropylamine and 257 ml of tetrahydrofuran was added 107 ml of a 2.64 M hexane solution of n-butyllithium under stirring while cooling the mixture in a dry ice-acetone bath, then, the mixture was stirred for 1.5 hours. Then, 25.0 g of 3-fluoropyridine was added, and the mixture was further stirred for 1.5 hours. Crushed dry ice was added to the reaction mixture, then, cooling was stopped, and the mixture was stirred until returning to room temperature. Water was added, and most of hexane and tetrahydrofuran were distilled off under reduced pressure. The residue was washed with tert-butyl methyl ether, and the aqueous layer was recovered. To the resultant aqueous layer was added concentrated hydrochloric acid under ice cool, and pH of the mixture was adjusted to 3 and the mixture was stirred for 1 hour. The deposit was collected by filtration, and dried under reduced pressure to obtain 32.51 g of 3-fluoroisonicotinic acid.

1. temperaturewhile cooling the mixture in a dry ice-acetone bath
2. stirringthe mixture was stirred for 1.5 hours
3. stirringthe mixture was further stirred for 1.5 hours
4. temperaturecooling
5. stirringthe mixture was stirred
6. customuntil returning to room temperature
7. distillationmost of hexane and tetrahydrofuran were distilled off under reduced pressure
8. washThe residue was washed with tert-butyl methyl ether
9. customthe aqueous layer was recovered
10. additionTo the resultant aqueous layer was added concentrated hydrochloric acid under ice
11. temperaturecool
12. stirringthe mixture was stirred for 1 hour
13. filtrationThe deposit was collected by filtration
14. customdried under reduced pressure

ORD record

ord-ebf6f04e7079420e868b49b2430566b4

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08273764B2