反应详情

温度

70 °C

A stirred mixture of 5-chloro-thiophene-2-boronic acid (5.15 g, 0.0317 mol), 4-(4-bromo-phenyl)-4-oxo-butyric acid, methyl ester (8.00 g, 0.0294 mol), and tetrakis(triphenylphosphine)palladium(0) (1.09 g, 0.00094 mol) in a two-phase mixture of toluene (62 mL) and 2.0 M aqueous sodium carbonate (31 mL, 0.062 mol) was heated at 70° C. for 20 hours and allowed to cool to room temperature. Additional 5-chloro-thiophene-2-boronic acid (0.369 g, 0.00227 mol) was added, and the mixture was reheated at 65° C. for 20 hours. The mixture was cooled to room temperature and filtered through Celite, eluting with dichloromethane. Filtrate and washings were combined, and the mixture was washed with 0.10 M aqueous sodium hydroxide (100 mL), 3% aqueous ammonium hydroxide (100 mL), water, and brine. The organics were dried (Na2SO4), and rotary evaporated to a solid. The residue was dissolved in chloroform. silica gel (101 g, 230-400 mesh) was added, and the mixture was rotary evaporated to dryness. The residue was purified by chromatography on silica gel (1450 g, 230-400 mesh), eluting with hexanes-acetone (12:1, 16×1L; 9:1, 12×1L) to give 6.04 g of 4-[4-(5-chloro-thiophen-2-yl)-phenyl]-4-oxo-butyric acid, methyl ester as a bright yellow solid; mp 117-118° C.

1. temperatureto cool to room temperature
2. temperatureThe mixture was cooled to room temperature
3. filtrationfiltered through Celite
4. washeluting with dichloromethane
5. washthe mixture was washed with 0.10 M aqueous sodium hydroxide (100 mL), 3% aqueous ammonium hydroxide (100 mL), water, and brine
6. dry with materialThe organics were dried (Na2SO4)
7. customrotary evaporated to a solid
8. dissolutionThe residue was dissolved in chloroform
9. additionsilica gel (101 g, 230-400 mesh) was added
10. customthe mixture was rotary evaporated to dryness
11. customThe residue was purified by chromatography on silica gel (1450 g, 230-400 mesh)
12. washeluting with hexanes-acetone (12:1, 16×1L; 9:1, 12×1L)