反应详情

温度

80 °C

In a 250 mL round-bottomed dried flask , diacetoxypalladium (0.036 g, 0.16 mmol) was treated with 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (0.195 g, 0.31 mmol) under nitrogen in toluene (35 mL). The reaction was heated to 80 °C and was stirred for 10 min. To the flask was then added tert-butyl piperazine-1-carboxylate (0.602 g, 3.23 mmol), cesium carbonate (0.527 g, 1.62 mmol), potassium carbonate (0.447 g, 3.23 mmol) and 1,4,7,10,13,16-hexaoxacyclooctadecane (0.085 g, 0.32 mmol). The reaction was then treated with 4-bromo-2-chlorobenzonitrile (0.7 g, 3.23 mmol) and was allowed to stir at 80°C for 5 h. The mixture was then filtered over celite and celite was washed with heptanes. The mixture was condensed under reduced pressure and the crude material was purified on preparative HPLC MS using the short high pH shallow gradient method (Mobile phase: 50-70% B; A: H2O with 10 mM NH4CO3 and 0.375% NH4OH v/v, B: CH3CN, 10 min run) on XBridge Prep C18 OBD, 30x50 mm, 5 mm, Waters reverse phase column, to afford tert-butyl 4-(3-chloro-4-cyanophenyl)piperazine-1-carboxylate (0.490 g, 47.1 %) as a white solid.