反应详情

A solution of 4-bromo-3-fluorobenzene sulphonyl chloride (10 g, 36.56 mmol) in THF (100 mL) was cooled to 0° C. and hydrazine monohydrate (6.2 mL, 127.96 mmol) was added dropwise. After the addition, the reaction was left to stir at room temperature for 1 hour before adding heptane (500 mL). The precipitate formed was filtered off and re-dissolved in industrial methylated spirit (200 mL). Sodium acetate (18 g, 219.36 mmol) was added followed by iodomethane (11.38 mL, 182.8 mmol). The reaction mixture was stirred at reflux for 18 hours. The reaction was cooled to room temperature and the solvent was concentrated to half of the initial volume. Water (300 mL) was added and the product was extracted with EtOAc (3×300 mL). The combined organic layers were washed with brine (300 mL) and dried (Na2SO4), filtered and concentrated under reduced pressure. The crude residue was purified by silica gel column chromatography eluting from 15% to 35% EtOAc/heptane to afford the title compound as a colourless solid in 48% yield, 4.40 g.

1. additionAfter the addition
2. waitthe reaction was left
3. customThe precipitate formed
4. filtrationwas filtered off
5. dissolutionre-dissolved in industrial methylated spirit (200 mL)
6. stirringThe reaction mixture was stirred
7. temperatureat reflux for 18 hours
8. temperatureThe reaction was cooled to room temperature
9. concentrationthe solvent was concentrated to half of the initial volume
10. additionWater (300 mL) was added
11. extractionthe product was extracted with EtOAc (3×300 mL)
12. washThe combined organic layers were washed with brine (300 mL)
13. dry with materialdried (Na2SO4)
14. filtrationfiltered
15. concentrationconcentrated under reduced pressure
16. customThe crude residue was purified by silica gel column chromatography
17. washeluting from 15% to 35% EtOAc/heptane