反应详情

Ethyl 5-bromo-2-chlorobenzoate (0.80 g, 3.04 mmol), rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (BINAP) (0.19 g, 0.30 mmol), tris(dibenzylideneacetone)dipalladium (Pd2(dba)3) (0.28 g, 0.30 mmol) and cesium carbonate (Cs2CO3) (1.39 g, 4.26 mmol) were placed in a Schlenk tube and purged by repeated nitrogen/vacuum cycles for 30 minutes. Dry toluene (6 mL) and 1-(2-dimethylaminoethyl)piperazine (0.55 mL, 3.65 mmol) were then added. The reaction mixture was stirred for 10 min at room temperature, heated at 85° C. overnight and then cooled to room temperature. The solution was diluted with EtOAc (30 mL), the insoluble material was filtered off and the filtrate was washed with saturated brine (15 mL). The organic phase was dried over Na2SO4, filtered and concentrated under reduced pressure to obtain a residue that was purified by flash chromatography (eluent gradient: EtOAc, EtOAc:MeOH/1:1, EtOAc:MeOH:NH3 in MeOH (2M)/1:1:0.2) to afford 0.30 g of the title compound (30%). 1H-NMR (400 MHz, DMSO): δ 1.28 (3H, t), 2.12 (6H, s), 2.32-2.42 (4H, m), 2.47-2.51 (4H, m), 3.11-3.14 (4H, m), 4.27 (2H, q), 7.06-7.09 (1H, m), 7.18-7.19 (1H, m), 7.30-7.32 (1H, m).

1. custompurged by repeated nitrogen/vacuum cycles for 30 minutes
2. temperatureheated at 85° C. overnight
3. temperaturecooled to room temperature
4. filtrationthe insoluble material was filtered off
5. washthe filtrate was washed with saturated brine (15 mL)
6. dry with materialThe organic phase was dried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customto obtain a residue that
10. customwas purified by flash chromatography (eluent gradient: EtOAc, EtOAc:MeOH/1:1, EtOAc:MeOH:NH3 in MeOH (2M)/1:1:0.2)