tert-Butyl piperazine-1-carboxylate → 3-(4-BOC-piperazino)-2-chloropyridine

Participants

Reaction Conditions

Reaction Steps

Dissolve 2-chloro-3-iodopyridine (2.0 g, 8.37 mmol) in toluene (7 mL). Add piperazine-1-carboxylic acid t-butyl ester (1.2 g, 6.4 mmol), followed by the addition of tris(dibenzylideneacetone)dipalladium(0) (0.12 g, 0.13 mmol), 4,5-bis(diphenyl-phosphino)-9,9-dimethylxanthene (0.23 g, 0.39 mmol), and sodium t-butoxide (0.93 g, 9.7 mmol). Heat at 100° C. for 3.5 hr. Concentrate and partition the residue between EtOAc and water. Extract the aqueous phase twice with ethyl acetate. Wash combined organic layers with brine. Dry the organic extracts (sodium sulfate), filter, concentrate and purify (silica gel chromatography, eluting with 0:100 to 20:80 ethyl acetate:hexanes), to give 4-(2-Chloro-pyridin-3-yl)-piperazine-1-carboxylic acid t-butyl ester (95%). MS (ES): m/z=298 [M+H]+.

Provenance & Evidence