反应详情

温度

90 °C

To a solution of tert-butyl 3-[5-acetyl-4-(4-fluorophenyl)-1H-imidazol-1-yl]azetidine-1-carboxylate (C3) (5.6 g, 15.6 mmol) in n-propanol (50 mL) was added N,N-dimethylformamide dimethyl acetal (12 g, 100 mmol), and the reaction mixture was stirred at 90° C. for 3 hours. At this point, guanidine hydrochloride (7.2 g, 75 mmol) and potassium carbonate (10 g, 72 mmol) were added to the reaction mixture. After stirring at 92° C. for an additional 16 hours, the reaction was treated with aqueous sodium hydroxide solution (5 N, 10 mL, 50 mmol), and stirring was continued for 16 hours at 92° C. After concentration in vacuo, the residue was partitioned between ethyl acetate (100 mL) and water (100 mL), and the aqueous phase was extracted with ethyl acetate (2×100 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude material was purified via silica gel chromatography (Eluant: 1:1 to 1:2 petroleum ether: ethyl acetate) to afford the product as a solid. Yield: 2.1 g, 5.1 mmol, 33%. NMR data was obtained from the product of a reaction run under similar conditions. 1H NMR (400 MHz, CD3OD) δ 1.46 (s, 9H), 4.22 (dd, J=9, 5 Hz, 2H), 4.41 (dd, J=9, 9 Hz, 2H), 5.47 (m, 1H), 6.39 (d, J=5.1 Hz, 1H), 7.10 (dd, J=8.7, 8.7 Hz, 2H), 7.42-7.47 (m, 2H), 8.09 (d, J=5.3 Hz, 1H), 8.25 (s, 1H).

1. stirringAfter stirring at 92° C. for an additional 16 hours
2. stirringstirring
3. waitwas continued for 16 hours at 92° C
4. concentrationAfter concentration in vacuo
5. customthe residue was partitioned between ethyl acetate (100 mL) and water (100 mL)
6. extractionthe aqueous phase was extracted with ethyl acetate (2×100 mL)
7. dry with materialThe combined organic layers were dried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customThe crude material was purified via silica gel chromatography (Eluant: 1:1 to 1:2 petroleum ether: ethyl acetate)