Tert-butyl 2,5-diazabicyclo[2.2.2]octane-2-carboxylate

24424-99-5

1192-92-3

858671-91-7

The general procedure for the synthesis of tert-butyl 2,5-diazabicyclo[2.2.2]octane-2-carboxylate from di-tert-butyl dicarbonate (6.5 mmol) and 2,5-diazabicyclo[2.2.2]octane dihydrochloride (7.06 mmol) is as follows: a solution of isopropanol (15 mL) of di-tert-butyl dicarbonate is slowly added dropwise to a solution of isopropanol (100 mL), water (35 mL), and 1M sodium hydroxide solution (6.5 mL) at 0°C, containing 2,5-diazabicyclo[2.2.2]octane dihydrochloride. bicyclo[2.2.2]octane dihydrochloride in a mixture of isopropanol (100 mL), water (35 mL) and 1M sodium hydroxide solution (6.5 mL). The reaction mixture was stirred at 0°C for 1.5 h and then concentrated to about 50 mL. Subsequently, the aqueous phase was saturated with solid sodium chloride and the pH was adjusted to 10 with 2 M sodium hydroxide solution. the aqueous phase was extracted with ethyl acetate (3 x 35 mL) and the combined organic layers were washed with brine and dried with magnesium sulfate. Finally, the solvent was removed by distillation under reduced pressure to afford the crude product tert-butyl 2,5-diazabicyclo[2.2.2]octane-2-carboxylate in 42% yield as a light yellow oil.