反应详情

温度

110 °C

Under a nitrogen atmosphere a mixture of 5-bromo-6-(2-methoxyethoxy)-pyridine-2-carboxylic acid methyl ester (Example 142 b, 0.42 g, 1.45 mmol), 3,3-difluoroazetidine hydrochloride (0.22 g, 1.74 mmol), tris(dibenzylideneacetone)dipalladium (CAN 51364-51-3, 27 mg, 0.03 mmol), (R)-(+)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (CAN 76189-55-4, 36 mg, 0.06 mmol) and cesium carbonate (1.4 g, 4.35 mmol) in toluene (50 mL) was stirred at 110° C. overnight. After evaporation of solvents the residue was partitioned between water (30 mL) and ethyl acetate (30 mL) and the aqueous phase was extracted with ethyl acetate (2×30 mL). The combined organic phase was washed with brine (30 mL), dried over anhydrous sodium sulfate, filtered and concentrated to give a residue which was purified by column chromatography (silica gel, 8 g, 15% ethyl acetate in petroleum ether) to give the title compound (0.3 g, 68%) as white solid; MS (EI): m/e=303.1 [M+H]+.

1. customAfter evaporation of solvents the residue
2. customwas partitioned between water (30 mL) and ethyl acetate (30 mL)
3. extractionthe aqueous phase was extracted with ethyl acetate (2×30 mL)
4. washThe combined organic phase was washed with brine (30 mL)
5. dry with materialdried over anhydrous sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. customto give a residue which
9. customwas purified by column chromatography (silica gel, 8 g, 15% ethyl acetate in petroleum ether)