反应详情

To a solution of 1-bromo-3,5-difluorobenzene (8 g, 41.4 mmol) in dry tetrahydrofuran (100 ml), under nitrogen, was added magnesium turnings (0.99 g, 41.4 mmol) and one crystal of iodine. The mixture was refluxed for 1 h, cooled to ambient temperature and a solution of 1-N-boc-3-pyrrolidone (7.66 g, 41.4 mmol) in dry tetrahydrofuran (40 ml) was added drop wise. The resulting mixture was refluxed 1 h, cooled to ambient temperature, aqueous saturated ammonium chloride solution (50 ml) was added and the mixture was extracted with ethylacetate (3×50 ml). The combined organic phase was washed with brine, dried (Na2SO4), filtered and evaporated to dryness. The crude product was purified by flash column chromatography (ethylacetate/isooctane, 1:9 to 1:1) to give the title compound (3.8 g, 30%). MS m/z (rel. intensity, 70 eV) 299 (M+, 1), 243 (30), 198 (39), 127 (36), 57 (bp).

1. temperatureThe mixture was refluxed for 1 h
2. temperatureThe resulting mixture was refluxed 1 h
3. temperaturecooled to ambient temperature
4. extractionthe mixture was extracted with ethylacetate (3×50 ml)
5. washThe combined organic phase was washed with brine
6. dry with materialdried (Na2SO4)
7. filtrationfiltered
8. customevaporated to dryness
9. customThe crude product was purified by flash column chromatography (ethylacetate/isooctane, 1:9 to 1:1)