Hydrochloric Acid → N-t-Butyl-3-fluoro-2-pyridinecarboxamiide

温度

100 °C

Dimethyl sulfate (1.01 g, 8 mmol) was added to 1-oxido-3-fluoropyridine (0.9 g, 8 mmol) and stirred at 100° C. for 2 hours. The reaction mixture was allowed to cool and concentrated to dryness under a reduced pressure. Water (10 ml) was added to the residue and cooled in an ice-bath. Sodium cyanide (1.18 g, 24 mmol) was added to the mixture and stirred for 30 min. followed by stirring at room temperature for 30 min. Aqueous NaOH (1N) was added thereto and extracted with chloroform. The extract was dried over Na2SO4 and the solvent was evaporated under a reduced pressure to give a mixture of regio-isomers of fluorocyanopyridine (0.9 g). Aqueous NaOH (4N, 10 ml) was added to the mixture of regio-isomers and heated under reflux for 2.5 hours. The mixture was allowed to cool, acidified with conc. hydrochloric acid and concentrated to dryness under a reduced pressure. The residue was suspended in DMF (10 ml), and t-butylamine (1.46 g, 20 mmol), WSC HCl (3.1 g, 16 mmol) and HOBt (2.2 g, 16 mmol) were added thereto and stirred overnight. The reaction mixture was diluted with water and extracted with ethyl acetate. The extract was washed with saturated aqueous NaHCO3 and dried over Na2SO4. The solvent was evaporated under a reduced pressure and the residue was purified by silica gel chromatography (hexane/ethyl acetate=5/1) to give the title compound (0.19 g; 12%).

1. temperatureto cool
2. concentrationconcentrated to dryness under a reduced pressure
3. additionWater (10 ml) was added to the residue
4. temperaturecooled in an ice-bath
5. stirringstirred for 30 min.
6. stirringby stirring at room temperature for 30 min
7. extractionextracted with chloroform
8. dry with materialThe extract was dried over Na2SO4
9. customthe solvent was evaporated under a reduced pressure
10. customto give
11. temperatureheated
12. temperatureunder reflux for 2.5 hours
13. temperatureto cool
14. concentrationconcentrated to dryness under a reduced pressure
15. stirringstirred overnight
16. extractionextracted with ethyl acetate
17. washThe extract was washed with saturated aqueous NaHCO3
18. dry with materialdried over Na2SO4
19. customThe solvent was evaporated under a reduced pressure
20. customthe residue was purified by silica gel chromatography (hexane/ethyl acetate=5/1)

ORDレコード

ord-7d02828bac4642549f59b800539e47a3

出典データセット

uspto-grants-2005_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US06936736B2