反应详情

温度

25 °C

810 g of 4-(3-chloro-4-fluoro-phenylamino)-7-(phenylsulphonyl)-6-nitro-quinazoline and 175.5 g (S)-3-hydroxytetrahydrofuran (1.3 eq) are placed at 20° C. in 1.04 l tert-butanol and 198 ml DMF, 2556 g K-tert.-butoxide in THF (24%) (3.6 eq) are added dropwise at 20° C. and then stirred for 4 h at 25° C. After a further 2 h at 40° C. the mixture is heated to 45° C. for about 2 h. 2.8 l of water are added and then about 3 l solvent are distilled off under reduced pressure. 2.8 l water are added again and about 900 ml solvent are distilled off under reduced pressure. After the addition of 1.6 l methanol the mixture is cooled to 20° C. The suspension is suction filtered and rinsed with a mixture of 3.2 l water and 1.6 l methanol. The residue is dried overnight at 50° C. under reduced pressure.

1. temperatureAfter a further 2 h at 40° C. the mixture is heated to 45° C. for about 2 h
2. distillationabout 3 l solvent are distilled off under reduced pressure
3. addition2.8 l water are added again
4. distillationabout 900 ml solvent are distilled off under reduced pressure
5. additionAfter the addition of 1.6 l methanol the mixture
6. temperatureis cooled to 20° C
7. filtrationsuction filtered
8. washrinsed with a mixture of 3.2 l water and 1.6 l methanol
9. customThe residue is dried overnight at 50° C. under reduced pressure