反应详情

温度

100 °C

A mixture of 5-cyclopropyl-2-(4-fluorophenyl)-N-methyl-6-(methylsulfonamido)benzofuran-3-carboxamide (12.5 g, 31.1 mmol), 2-chloro-4-fluoronitrobenzene (10.9 g, 62.1 mmol) and potassium carbonate (12.9 g, 93.0 mmol) in 130 mL of 4:1 DME/water in a sealed flask was heated to 100° C. with stirring. An identical 12.5 g scale reaction was set up in a second sealed vessel. The reaction vessels were maintained at 100° C. for 70 hours, cooled to RT, and stirred for an additional 18 hours. The combined reaction mixtures were partitioned between EtOAc (300 mL) and water (600 mL), and the phases separated. The aqueous solution was extracted with two additional 150 mL portions of EtOAc. The combined EtOAc solutions were washed with half saturated brine (1×), saturated brine (1×), dried over sodium sulfate and concentrated to dryness at reduced pressure. The resulting yellow-brown solid was recrystallized from EtOAc/ether to give the title compound (22.3 g, 64%) as an off-white solid. LCMS (m/z, ES+)=558 (M+H+).

1. customAn identical 12.5 g scale reaction
2. customwas set up in a second sealed vessel
3. customThe reaction vessels
4. temperaturewere maintained at 100° C. for 70 hours
5. temperaturecooled to RT
6. stirringstirred for an additional 18 hours
7. customThe combined reaction mixtures
8. customwere partitioned between EtOAc (300 mL) and water (600 mL)
9. customthe phases separated
10. extractionThe aqueous solution was extracted with two additional 150 mL portions of EtOAc
11. washThe combined EtOAc solutions were washed with half saturated brine (1×), saturated brine (1×)
12. dry with materialdried over sodium sulfate
13. concentrationconcentrated to dryness at reduced pressure
14. customThe resulting yellow-brown solid was recrystallized from EtOAc/ether