Hydroquinone → Tert-butyl 4-(pyridin-4-yl)piperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

Dichloromethane (0.1 ml) was added to a suspension of zinc (2 g, 31.7 mmol) in N,N-dimethylformamide (5 ml), and the mixture warmed until gas evolution occurred. tert-Butyl 4-iodo-1-piperidinecarboxylate (EP 1078928) (4.9 g, 15.8 mmol), and hydroquinone (35 mg, 0.32 mmol) in N,N-dimethylformamide (5 ml) was added, and the mixture warmed until an exotherm was evident. 4-Bromopyridine (1 g, 6.33 mmol), tris(dibenzylideneacetone)dipalladium (0) (73 mg, 0.127 mmol) and tri(2-furyl)phosphine (59 mg, 0.25 mmol) in N,N-dimethylformamide (5 ml) were added, and the reaction stirred at 60° C. for 30 minutes. The cooled mixture was partitioned between water (100 ml) and diethyl ether (50 ml), and the layers separated. The aqueous phase was extracted with diethyl ether (2×50 ml), the combined organic solutions washed with brine (50 ml), dried (MgSO4) and evaporated under reduced pressure, to give a brown oil. This was purified by column chromatography on silica gel using ethyl acetate:pentane (50:50) as eluant to afford the title compound as a yellow oil, 1.1 g.

Provenance & Evidence