反应详情

To the suspension of 2-chloro-5-fluoropyridine-3-carboxylic acid (37.0 g, 210.8 mmol) in dichloromethane (555 mL) was added oxalyl chloride (56.2 g, 442.7 mmol) under nitrogen. DMF (1.54 g, 21.08 mmol) was added slowly to the reaction mixture. The mixture was stirred at room temperature for 2 hr and dichloromethane was removed under reduced pressure. The residue was dissolved in THF (300 mL) and cooled down to 0° C. by ice bath. Ammonium hydroxide (28-30%, 113.0 mL, 1.8 mmol) was added in one portion. The mixture was stirred for another 15 min. The mixture was diluted into ethyl acetate (300 mL) and water (300 mL) and the phases were separated. The organic layer was washed with brine and dried over Na2SO4, filtered, and concentrated in vacuo to afford 29.8 g desired product as white solid: 1H NMR (300 MHz, DMSO) δ 8.53 (d, J=3.0 Hz, 1H), 8.11 (s, 1H), 8.00 (dd, J=8.0, 3.0 Hz, 1H), 7.89 (s, 1H); LC/MS Gradient 10-90%, 0.1% formic 5 min, C18/ACN, RT=1.11 min, (M+H) 175.02.

1. customdichloromethane was removed under reduced pressure
2. dissolutionThe residue was dissolved in THF (300 mL)
3. temperaturecooled down to 0° C. by ice bath
4. stirringThe mixture was stirred for another 15 min
5. customthe phases were separated
6. washThe organic layer was washed with brine
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated in vacuo