反应详情

Cool a mixture of ethyl 5-(aminomethyl)-2-(difluoromethyl)pyridine-3-carboxylate dihydrochloride (29.8 g, 111.8 mmol, 1.0 equiv), DCM (510 mL), and triethylamine (59.2 mL, 424.6 mmol, 3.8 equiv) to 0° C., then add a solution of isobutyryl chloride (15.3 mL, 145.3 mmol, 1.3 equiv) in DCM (23 mL) drop wise over 20 min. Stir overnight while allowing the mixture to warm to room temperature. Remove the solid precipitate by filtration, and rinse the filter with EtOAc (500 mL). Concentrate the filtrate under reduced pressure; filter the concentrate to remove the solids; and rinse the solids with EtOAc. Concentrate the filtrate under reduced pressure to give a yellow oil. Subject this crude material to silica gel chromatography eluting with a gradient of 40-90% EtOAc/hexanes gradient, to give the title compound as a light yellow crystalline solid (25.8 g, 77% yield). ES/MS (m/z) 301 (M+1).

1. temperatureCool
2. customRemove the solid precipitate
3. filtrationby filtration
4. washrinse the
5. filtrationfilter with EtOAc (500 mL)
6. concentrationConcentrate the filtrate under reduced pressure
7. filtrationfilter the
8. concentrationconcentrate
9. customto remove the solids
10. washand rinse the solids with EtOAc
11. concentrationConcentrate the filtrate under reduced pressure
12. customto give a yellow oil
13. washeluting with a gradient of 40-90% EtOAc/hexanes gradient