反应详情

温度

80 °C

1-chloro-2-fluoro-4-methoxy-5-nitrobenzene (3.05 g, 14.83 mmol) and dimethyl malonate (2.5 g, 18.84 mmol) were added to N-methylpyrrolidinone (50 mL) at room temperature. Sodium hydroxide (1.25 g, 31.14 mmol) was added and the temperature was raised to 80° C. and maintained for 2 hours. The reaction mass was cooled to 5° C. then 1 N HCl solution was added to adjust the pH to 2. Water (300 mL) was added and the mixture stirred for 15 minute at 5° C. The precipitate was collected by filtration, washed with water (2×10 mL), dissolved in DCM (60 mL), dried (Na2SO4) and the solvent removed under reduced pressure. The residue was purified by column chromatography on neutral silica gel using 10-20% EtOAc in hexane to give the title compound (3.2 g, 68%) as a solid.

1. temperaturemaintained for 2 hours
2. temperatureThe reaction mass was cooled to 5° C.
3. filtrationThe precipitate was collected by filtration
4. washwashed with water (2×10 mL)
5. dissolutiondissolved in DCM (60 mL)
6. dry with materialdried (Na2SO4)
7. customthe solvent removed under reduced pressure
8. customThe residue was purified by column chromatography on neutral silica gel using 10-20% EtOAc in hexane