Dichloromethane → HCID 67135214, compound

Participants

Reaction Steps

tert-Butyl 4-(5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)piperidine-1-carboxylate 2-Methyl-2,5-diazabicyclo[2.2.1]heptane dihydrobromide (1.715 mmol, 1 eq.), tert-butyl 4-oxopiperidine-1-carboxylate (2.401 mmol, 1.4 eq.) and triethylamine (4.288 mmol, 2.5 eq.) were dissolved in dichloromethane (120 mmol, 70 eq.) and the resulting mixture was stirred for 5 min at RT under nitrogen. Subsequently sodium triacetoxy borohydride (2.401 mmol, 1.4 eq.) was added and the mixture stirred for 16 h at RT. Ethyl acetate (30 ml) and sat. aq. sodium hydrogen carbonate solution (30 ml) were added to the reaction mixture and it was stirred for 15 min. The phases were separated and the aqueous phase was extracted with ethyl acetate (3×30 ml). The combined organic layers were dried over MgSO4 and concentrated in vacuo. The crude product was purified by column chromatography (ethyl acetate/methanol/DCM, 10:10:5+25% aq ammonia) to yield the title compound. Yield: 0.35 g (69%) 2. 2-Methyl-5-(piperidin-4-yl)-2,5-diazabicyclo[2.2.1]heptane dihydrochloride Tert-butyl 4-(5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)piperidine-1-carboxylate (1.158 mmol, 1 eq.) was dissolved in Ethanol (7 ml) and acetyl chloride (5.76 mmol, 5 eq.) was added at 0° C. The mixture was stirred at RT for 16 h, at which time a light solid had precipitated. The suspension was diluted with diethyl ether (30 ml) and the solid was collected by filtration and washed with diethyl ether (50 ml). The title compound thus obtained was dried under high vacuum. Yield: 0.34 g (>99%)

Provenance & Evidence