Guanidine Hydrochloride → HCID 57461719, compound

Participants

Reaction Conditions

Reaction Steps

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).

Provenance & Evidence