反应详情

In a 250 mL round bottomed flask were placed 2-bromo-6,7-dihydro-1-benzothiophen-4(5H)-one (3.69 g, 16.0 mmol), pyridine-4-boronic acid (3.0 g, 24.5 mmol), and then suspended in 1,4-dioxane (50 mL). To the mixture were added cesium carbonate (18.7 g, 57.3 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (910 mg, 1.1 mmol) and water (50 mL). The mixture was refluxed for 16 h with vigorous stirring. The mixture was allowed to cool to rt and was then diluted with EtOAc (100 mL), which was washed with water (50 mL) and brine (50 mL). Insoluble materials were removed by filtration through Celite pad. The combined aqueous phase was extracted with EtOAc (50 mL). The combined organic phase was dried over anhydrous MgSO4 and insoluble materials were removed by filtration. The filtrate was concentrated under reduced pressure and the residue was purified by prepacked silica gel (120 g) column chromatography eluted with a 50% to 100% EtOAc/hexane. Concentration of appropriate fractions afforded colorless crystalline solid which was suspended in ether (50 mL) and then stirred for 15 min and then ultra-sonicated. The remaining crystalline materials were collected by filtration to obtain the title compound (2.6 g; 71%). From mother liquid, 2nd crop of the title compound (760 mg; 21%) has been obtained. LCMS: (FA) ES+ 230. 1H NMR (300 MHz, d6-DMSO) δ: 8.57 (dd, 2H), 7.95 (s, 1H), 7.67 (dd, 2H), 3.08 (2H, t), 2.50-2.54 (m, 2H), 2.10-2.19 (m, 2H).

1. customIn a 250 mL round bottomed flask were placed
2. temperatureThe mixture was refluxed for 16 h with vigorous stirring
3. washwas washed with water (50 mL) and brine (50 mL)
4. customInsoluble materials were removed by filtration through Celite pad
5. extractionThe combined aqueous phase was extracted with EtOAc (50 mL)
6. dry with materialThe combined organic phase was dried over anhydrous MgSO4 and insoluble materials
7. customwere removed by filtration
8. concentrationThe filtrate was concentrated under reduced pressure
9. customthe residue was purified by prepacked silica gel (120 g) column chromatography
10. washeluted with a 50% to 100% EtOAc/hexane
11. customConcentration of appropriate fractions afforded colorless crystalline solid which
12. customultra-sonicated
13. filtrationThe remaining crystalline materials were collected by filtration