反应详情

Dissolve ethyl 2-(difluoromethyl)-5-{[(2-methylpropanoyl)amino]methyl}pyridine-3-carboxylate (414 g, 1.38 mol, 1.0 equiv) in 1,4-dioxane (4.97 L). Add water (2.48 L) and lithium hydroxide (125.6 g, 2.96 mol, 2.5 equiv); then stir the resulting mixture for 60 min at room temperature. Concentrate the 1,4-dioxane solution to ½ volume under reduced pressure, and add hydrochloric acid (5 N, 1.16 L, 5.79 mol, 4.2 equiv) slowly to maintain temperature at less than 20° C. until the pH is 2. Collect the solids by filtration; air dry for 18 hours; and then in a vacuum oven at 40° C. for 18 hours to give a white solid, (355.4 g, 94.7% yield). MS (m/z) 303 (M+1).

1. concentrationConcentrate the 1,4-dioxane solution
2. temperatureto maintain temperature at less than 20° C. until the pH is 2
3. customCollect the solids
4. filtrationby filtration
5. customair dry for 18 hours
6. customand then in a vacuum oven at 40° C. for 18 hours to give a white solid, (355.4 g, 94.7% yield)