Carbon Dioxide → 3-Bromoisonicotinic acid

A mixture of 3.54 g of diisopropylamine and 50 ml of tetrahydrofuran was stirred while cooling in a dry ice-acetone bath. To the reaction mixture, 20 ml of 1.6 M hexane solution of n-butyllithium was added so that the temperature of the reaction mixture did not exceed −40° C. The reaction mixture was stirred for 30 minutes. Then, a mixture of 4.74 g of 3-bromopyridine and 5 ml of tetrahydrofuran was added so that the temperature of the reaction mixture did not exceed −60° C. The reaction mixture was stirred for further 30 minutes. Crushed dry ice was added to the reaction mixture and then cooling was stopped. The reaction mixture was stirred until the temperature returned to room temperature. Water was added thereto, most 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 layers, concentrated hydrochloric acid was added while ice-cooling so that pH of the mixture was made to be 3 and stirred for one hour, followed by extraction with ethyl acetate three times. The combined organic layers were washed with a saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give 0.69 g of 3-bromo isonicotinic acid.

1. temperaturewhile cooling in a dry ice-acetone bath
2. customdid not exceed −40° C
3. stirringThe 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 reaction mixture was stirred for further 30 minutes
7. temperaturecooling
8. stirringThe reaction mixture was stirred until the temperature
9. customreturned to room temperature
10. custommost of hexane and tetrahydrofuran was removed under reduced pressure
11. washThe residue was washed with tert-butyl methyl ether
12. customthe aqueous layers were collected
13. additionTo the collected aqueous layers, concentrated hydrochloric acid was added while ice-
14. temperaturecooling so that pH of the mixture
15. stirringstirred for one hour
16. extractionfollowed by extraction with ethyl acetate three times
17. washThe combined organic layers were washed with a saturated sodium chloride solution
18. dry with materialdried over anhydrous sodium sulfate
19. concentrationconcentrated under reduced pressure

ORD record

ord-20e69a9c611343fd86120b778bc3d4c2

Source dataset

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08445522B2