反应详情

P2O5 (90 grams) was added in portions to H3PO4 (90 grams) while maintaining the temperature below 140° C. The mixture was heated at 115° C. for 1.5 hour, whereupon 3-[2-(4-chloro-phenoxy)-phenyl]-1-methyl-pyrrolidine-2,4-dione (XI) (30 grams; 95 mmol) was added. The resulting mixture was stirred for 4 days at 115° C. to 130° C. with extra P2O5 (in total 5 portions of 5 grams each were added). The mixture was poured into water (200 ml) and the resulting precipitate was stirred overnight. The mixture was extracted with dichloromethane (250 ml) and washed with sat. NaHCO3 (pH=7). After drying on magnesium sulphate the solvent was removed under vacuum. The resulting crude product was dissolved in methanol (520 ml) at 70° C. Following removal of part of the methanol by evaporation the product crystallized. The mixture was stirred overnight at −12° C. The crystals were filtered and dried to provide 5-chloro-2,3-dihydro-2-methyl-1H-dibenz [2,3;6,7]oxepino[4,5-c]pyrrol-1-one (VI) (16.4 grams, 55 mmol; 58%), purity according to GC 92%. 1H-NMR (400 MHz, CDCl3): 3.2 (s, 3H), 4.3 (s, 1H), 3.8 (m, 1H), 7.2-7.4 (m, 6H), 8.2 (dd, 1H).

1. temperaturewhile maintaining the temperature below 140° C
2. additionwas added
3. extractionThe mixture was extracted with dichloromethane (250 ml)
4. washwashed with sat. NaHCO3 (pH=7)
5. customAfter drying on magnesium sulphate the solvent
6. customwas removed under vacuum
7. dissolutionThe resulting crude product was dissolved in methanol (520 ml) at 70° C
8. customremoval of part of the methanol
9. customby evaporation the product
10. customcrystallized
11. stirringThe mixture was stirred overnight at −12° C
12. filtrationThe crystals were filtered
13. customdried