4-Bromopyridinium chloride → HCID 69426437, compound

Participants

Reaction Conditions

Reaction Steps

A suspension of 1-t-butoxycarbonyl-4-[(methylamino)methyl]piperidine (4.28 g, 18.8 mmol), 4-bromopyridine hydrochloride (4.82 g, 22.5 mmol) in 1,4-dioxane (60 mL) is degassed by sonication and passing argon through the mixture for 15 minutes. Sodium t-butoxide (5.77 g, 60.0 mmol), tris(dibenzylideneacetone) dipalladium (858 mg, 0.938 mmol) and tri-t-butyl phosphine (0.5M in toluene; 3 mL, 1.50 mmol) are added sequentially. The system is sealed, evacuated and back-filled with argon (×5), then heated at 60° C. for 48 hours. The mixture is poured onto a 1:1 mixture of water-ethyl acetate (4 mL), Celite™ is added and the mixture is filtered through a bed of Celite™. The phases are separated and the aqueous phase is extracted into ethyl acetate (×3). The combined organic extracts are washed with brine, dried (sodium sulfate), filtered and concentrated in vacuo. The residue is emulsified in water, potassium hydrogen sulfate is added until pH 2-3 and the aqueous phase is washed with ethyl acetate (×3). The aqueous phase is made basic by the addition of sodium hydroxide until pH >12 and extracted into ethyl acetate (×4). The combined organic extracts are washed with brine, dried (magnesium sulfate), filtered and concentrated in vacuo giving 1-t-butoxycarbonyl-4-{[(methyl)(pyridin-4-yl)amino]methyl}piperidine (5.23 g, 91%).

Provenance & Evidence