81% |
Stage #1: 4-Fluoronitrobenzene With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 25℃; for 2.33333h; Inert atmosphere;
Stage #2: 2,5-difluorophenol With copper(l) chloride In N,N-dimethyl-formamide; mineral oil at 100℃; for 12h; |
O.1
Step 1Into a 500 raL 3-necked round-bottom flask, was placed a solution of sodium hydride (3.9 g, 162.50 mrnol, 1.7 equiv) in N,N-dimethylformamide (200 mL). This was followed by the addition of a solution of l-fluoro-4-nitrobenzene ( 13.6 g, 96.39 mmol, 1.00 equiv) in N,N-dimethylformarnide (50 mL) dropwise with stirring at 0 °C over 20 min. The reaction mixture was stirred for 2 hr at 25 °C and then CuCl (9.6 g, 96.97 mmol, 1.0 equiv) was added, followed by addition of a solution of 2,5-difluorophenol ( 15.5 g, 1 19.15 mmol, 1 .2 equiv) in N,N-dimethylformamide (50 mL) dropwise with stirring at 25°C over 10 min. The resulting solution was stirred for 12 h at 100 °C in an oil bath and then diluted with water and washed with ether, water and brine. The reaction mixture was dried over anhydrous sodium sulfate and concentrated. The residue was loaded onto a silica get column and eluted with ethyl acetate/petroleum ether (1/8) to give 19.5 g (81 %) of l,4-difluoro-2-(4- nitrophenoxy)benzene as a brown solid, |
81% |
Stage #1: 4-Fluoronitrobenzene With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 25℃; for 2.33333h; Inert atmosphere;
Stage #2: 2,5-difluorophenol In N,N-dimethyl-formamide; mineral oil at 25 - 100℃; for 12.1667h; |
21.1
Step 1into a 500 mL 3 -necked round-bottom flask, was placed a solution of sodium hydride (3.9 g, 162.50 mmol, 1 .7 equiv) in N,N-dimethyiforniamide (200 mL). This was followed by the addition of a solution of 1 -fluoro-4-nitrobenzene (13.6 g, 96.39 mmol, 1.00 equiv) in N,N-dimethylformamide (50 mL) dropwise with stirring at 0 °C over 20 min. The reaction mixture was stirred for 2 hr at 25 °C and then CuCl (9.6 g, 96.97 mmol, 1.0 equiv) was added, followed by addition of a solution of 2,5-difluorophenol (15.5 g, 119.15 mmol, 1.2 equiv) in N,N-dimethylformamide (50 mL) dropwise with stirring at 25°C over 10 min. The resulting solution was stirred for 12 h at 100 °C in an oil bath and then diluted with water and washed with ether, water and brine. The reaction mixture was dried over anhydrous sodium sulfate and concentrated. The residue was loaded onto a silica gel column and eluted with ethyl acetate/petroleum ether (1/8) to give 19.5 g (81 %) of 1 ,4-difluoro -2-(4- nitrophenoxy)benzene as a brown solid, |
81% |
Stage #1: 4-Fluoronitrobenzene With sodium hydride In N,N-dimethyl-formamide at 0 - 25℃; for 2.33333h;
Stage #2: 2,5-difluorophenol With copper(l) chloride In N,N-dimethyl-formamide at 25 - 100℃; for 12h; |
14.1
Into a 500 ml. 3-necked roundbottom flask, was placed a solution of sodium hydride (3.9 g, 162.50 mmol, 1.7 equiv) in N,N-dimethylformamide (200 mL). This was followed by the addition of a solution of 1-fluoro-4-nitrobenzene (13.6 g, 96.39 mmol, 1 .00 equiv) in N,N-dimethylformamide (50 ml.) dropwise with stirring at 0°C over 20 mm. The reaction mixture was stirred for 2 hr at 25 °C and then CuCl (9.6 g, 96.97 mmol, 1.0 equiv) was added, followed by addition of a solution of 2,5-ifluorophenol (15,5 g, 119.15 mmol, 1.2 equiv) in N,Ndimethylformamide (50 ml.) dropwise with stirring at 25°C over 10 mm. The resulting solution was stirred for 12 h at 100 °C in an oil bath and then diluted with water and washed with ether, water and brine. The reaction mixture was dried over anhydrous sodium sulfate and concentrated. The residue was loaded onto a silica gel column and eluted with ethyl acetate/petroleum ether (1/8) to give 19.5 g (81%) of 1,4-difluoro-2-(4-nitrophenoxy)-benzene as a brown solid, |