Phosphoric Acid → 5-chloro-2-methyl-2,3-dihydro-1H-dibenzo[2,3:6,7]oxepino[4,5-c]pyrrol-1-one

Temperature

110 °C

Phosphorus pentoxide (270 g) is added in portions to H3PO4 (270 g) and the mixture is maintained for 1-2 hours at 100-120° C. 3-(2-(4-chlorophenoxy)phenyl)-1-methyl-pyrrolidine-2,4-dione (90 g) is added and the mixture is maintained for three days at 100-110° C. Additional P2O5 (30 g) is added in two portions and the mass is maintained for one day at 100-120° C. The mass is poured into water (900 mL) and the mass is stirred overnight at 25-35° C. The mass is extracted with dichloromethane (1000 mL), the layers are separated, and the aqueous layer is washed with dichloromethane (400 mL). The combined organic layer is washed with water (900 mL), 5% sodium bicarbonate (300 mL), and saturated brine solution (500 mL). After drying over anhydrous sodium sulfate, the solvent is removed under vacuum. The residue is dissolved in methanol (400 ml) and heated at reflux for 30-60 minutes. The solution is cooled to −10 to −15° C. and a solid forms. The solid is collected by filtration, washed with chilled methanol (50 mL), and dried to afford the title compound. Yield: 37.5 g. Purity by HPLC: 89.47%.

1. temperaturethe mixture is maintained for three days at 100-110° C
2. temperaturethe mass is maintained for one day at 100-120° C
3. extractionThe mass is extracted with dichloromethane (1000 mL)
4. customthe layers are separated
5. washthe aqueous layer is washed with dichloromethane (400 mL)
6. washThe combined organic layer is washed with water (900 mL), 5% sodium bicarbonate (300 mL), and saturated brine solution (500 mL)
7. dry with materialAfter drying over anhydrous sodium sulfate
8. customthe solvent is removed under vacuum
9. dissolutionThe residue is dissolved in methanol (400 ml)
10. temperatureheated
11. temperatureat reflux for 30-60 minutes
12. temperatureThe solution is cooled to −10 to −15° C.
13. filtrationThe solid is collected by filtration
14. washwashed with chilled methanol (50 mL)
15. customdried

ORD record

ord-d48a4a2f50e24ca8ad9f3f19e01dfe79

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08779161B2