反应详情

温度

90 °C

To a solution of 2.48 g (13.1 mmol) of the product prepared in step 10.1 in 26 mL of acetonitrile are added 2.43 g (13.1 mmol) of tert-butyl piperazinecarboxylate and 3.36 mL (19.65 mmol) of diisopropylethylamine. The reaction mixture is heated at 90°C. for 20 hours. It is diluted with ethyl acetate and washed with water and then with saturated aqueous NaCl solution. The crude solid is purified by chromatography on a column of silica, eluting with a cyclohexane/ethyl acetate gradient (85/15 to 50/50). A 3.25 g fraction predominantly containing the regioisomer tert-butyl 4-(5-fluoro-3-methoxy-2-nitrophenyl)piperazine-1-carboxylicate is isolated. An impure secondary fraction is purified again on a column of silica, eluting with a dichloromethane/ethyl acetate gradient (96/4 to 94/6). 0.985 g of expected product is finally obtained in the form of a yellow solid. Yield=21%.

1. washwashed with water
2. customThe crude solid is purified by chromatography on a column of silica
3. washeluting with a cyclohexane/ethyl acetate gradient (85/15 to 50/50)
4. additionA 3.25 g fraction predominantly containing the regioisomer tert-butyl 4-(5-fluoro-3-methoxy-2-nitrophenyl)piperazine-1-carboxylicate
5. customis isolated
6. customAn impure secondary fraction is purified again on a column of silica
7. washeluting with a dichloromethane/ethyl acetate gradient (96/4 to 94/6)