反应详情

Piperazine (20.0 g, 232.3 mmol) and K2CO3 (16.0 g, 118.5 mmol) are dissolved in CH3CN (85 ml). 2,4-Difluoro-benzonitrile (8.5 g, 61.1 mmol) is added and the mixture is stirred for 2 h at rt, then diluted with AcOEt and washed with water. The organic layer is separated, dried over Na2SO4 and evaporated. Excess piperazine is removed by MPLC (100 g silica gel, eluent CH2Cl2:MeOH 85:15). A second chromatographic purification (300 g silica gel, eluent toluene:EtOH:AcOH 4:4:1) yields the acetate salt of 2-fluoro-4-(piperazin-1-yl)-benzonitrile that is crystallized from AcOEt, filtered off and washed with ether. The free base is isolated by extraction with sat. aq. Na2CO3 solution/AcOEt.

1. washwashed with water
2. customThe organic layer is separated
3. dry with materialdried over Na2SO4
4. customevaporated
5. customExcess piperazine is removed by MPLC (100 g silica gel, eluent CH2Cl2:MeOH 85:15)
6. customA second chromatographic purification (300 g silica gel, eluent toluene:EtOH:AcOH 4:4:1)