3-Bromopyridine → tert-butyl (1S,4S)-5-(3-pyridinyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate

Participants

Reaction Conditions

Reaction Steps

TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (0.055 g, 0.06 mmol) and rac-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (0.075 g, 0.12 mmol) were mixed together and evacuated and purged with nitrogen 3 times. toluene (29.7 ml) was added and the resulting mixture heated to 90°C for 10 minutes then cooled to room temperature. In a second reaction vessel was mixed sodium tert-butoxide (0.465 g, 4.84 mmol), 3-bromopyridine (0.321 ml, 3.33 mmol) and (1S,4S)-tert-butyl 2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (0.601 g, 3.03 mmol) and toluene (29.7 ml). The mixture was evacuated and purged with nitrogen 3 times. The solution of catalyst was added to the reaction mixture and the resulting mixture was heated at 85 °C for 64 hours. The reaction mixture was cooled to RT and filtered through celite and concentrated to give an orange solid. The crude product was purified by flash silica chromatography, elution gradient 30 to 50% EtOAc in heptane. Then 100% MeOH. Pure fractions were evaporated to dryness to afford (1S,4S)-tert-butyl 5-(pyridin-3-yl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (0.823 g, 99 %) as a pale yellow dry film.

Provenance & Evidence