8-Benzyl-3-exo-(5-isopropyl-3-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octane

Chemical Properties

Brown Solid

Synthesis

A solution of N-(8-benzyl-8-aza-bicyclo[3.2.1]oct-3-yl)-isobutyramide in dichloromethane was slowly added to a slurry of phosphorous pentachloride in dichloromethane at 0 °C, and the mixture was allowed to warm to ambient temperature over 2 hours. The resulting solution was cooled to 0°C, and a solution of acetyl hydrazide in amyl alcohol was slowly added at 10 °C. The reaction was stirred at ambient temperature overnight. The mixture was then cooled to 0°C and treated with 2N sodium hydroxide at 20°C, and the pH was adjusted to 9 with 30% aqueous sodium hydroxide. The organic layer was separated and the aqueous layer was extracted with dichloromethane. The combined organic layers were dried and concentrated to about volume. Ethyl acetate and acetic acid were added and the mixture was heated to 80° C for 1 hour, cooled to ambient temperature and stirred overnight. The solution was cooled to 0°C and the pH was adjusted to about 12 with 2N sodium hydroxide. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were dried and concentrated to give 8-Benzyl-3-(3-isopropyl-5-methyl-4h-1,2,4-triazol-4-yl)-8-aza-bicyclo[3.2.1]octane. Yield: 65%.