反应详情

Add dropwise potassium tert-butoxide 1M in tetrahydrofuran (2.08 Kg, 2.08 mol) to a solution of ethyl 3-tert-butyl-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine-7-carboxylate (455 g, 1.81 mol) and 4-fluorobenzamidoxime (320 g, 2.08 mol) in tetrahydrofuran (11 L) at room temperature. Stir the reaction mixture for 16 hours. Pour the mixture over a solution of saturated sodium bicarbonate (6 L) and add brine (3×2 L). Separate phases and extract aqueous phase with ethyl acetate (3×1 L). Combine organics, dry over magnesium sulfate, filter, and concentrate to dryness under reduced pressure. Purify the resulting residue by silica gel chromatography eluting with ethyl acetate to ethyl acetate:methanol (9:1) to provide the title compound as a white solid (330 g). Mass spectrum (m/z): 342 (M+1).

1. extractionSeparate phases and extract aqueous phase with ethyl acetate (3×1 L)
2. dry with materialCombine organics, dry over magnesium sulfate
3. filtrationfilter
4. concentrationconcentrate to dryness under reduced pressure
5. customPurify the resulting residue by silica gel chromatography
6. washeluting with ethyl acetate to ethyl acetate:methanol (9:1)