tert-butyl 3,8-diazabicyclo[3.2.1]octane-3-carboxylate;hydrochloride

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: tert-Butyl 3,8-diazabicyclo[3.2.1]octane-3-carboxylate hydrochloride (1.36 g, 5.5 mmol; see Preparation A) was dissolved in H2O/CHCl3/saturated K2CO3 solution (40:40:5) and the resulting mixture was shaken. The phases were separated, dried and evaporated giving 1.1 g (100%), of the free base. Acetonitrile (100 mL), 4-(2-bromoethoxy)benzonitrile (1.49 g, 6.6 mmol; from step (a) above) and K2CO3 (2.4 g, 17.5 mmol) were added. The mixture was stirred at 70° C. for 24 h, the solids were filtered off and the residue evaporated and purified by chromatography on silica, eluting with CHCl3:MeOH (95:5), to give 1.5 g (4.3 mmol) of the sub-title compound. Preparation A) The phases were separated dried evaporated giving 1.1 g (100%) The mixture was stirred at 70° C. for 24 h the solids were filtered off the residue evaporated purified by chromatography on silica eluting with CHCl3:MeOH (95:5)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Palladium on carbon (10% w/w, 500 mg) was added to a solution of 8-benzyl-3-(tert-butoxycarbonyl)-3,8-diazabicyclo[3.2.1]octane hydrochloride (16.5 g, 48.0 mmol, see step (h) above) in methanol (250 mL) under a nitrogen atmosphere at 25° C. The nitrogen atmosphere was exchanged for a hydrogen atmosphere (1 atm of pressure) and the reaction was stirred rapidly. After 4 h the stirring was stopped and the reaction was filtered through a pad of Celite®. The filtrate was concentrated in vacuo to afford an off-white solid (11.6 g). The solid was slurried in acetonitrile, collected and dried in vacuo to afford 10.5 g (86%) of the title compound. the reaction was filtered through a pad of Celite® The filtrate was concentrated in vacuo