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

Participants

Reaction Conditions

Reaction Steps

Stir 2-chloro-3-bromopyridine (5.00 g, 26.0 mmol) and piperazine-1-carboxylic acid t-butyl ester (3.73 g, 20.0 mmol) in dry toluene (200 mL) at room temperature under nitrogen. Add sodium t-butoxide (2.88 g, 30.0 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.366 g, 0.40 mmol) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.694 g, 1.20 mmol), degas reaction and heat to 100° C. (oil bath temperature) for 3 hr. Cool to room temperature, add 100 mL water, extract with 2×200 mL ethyl acetate. Concentrate organic layer in vacuo, purify (silica gel chromatography, eluting with 30:70 ethyl acetate:isohexane) and dry in a vacuum oven over night to give 4-(2-chloro-pyridin-3-yl)-piperazine-1-carboxylic acid t-butyl ester as a beige powder (3.01 g, 51%). MS (m/z): 298 (M+1).

Provenance & Evidence