Hydrochloric Acid → 2-Chlorodibenz(b,f)-1,4-oxazepin-11(10H)-one

Temperature

60 °C

The crude product (2.8 g, 9.55 mmol) was then dissolved in THF (15 ml) and 2 M LiOH (40 mmol) was added. The reaction mixture was stirred at 60° C. for 2 h and then cooled to room temperature. THF was removed by rotary evaporation and the residue was acidified with HCl (2M) to a pH of 2 and filtered. The filter cake washed with 0.1M NaOH solution and finally dried to give the crude product 2.4 g (86%). Na2S2O4 (37 mmol) was added to a solution of the crude product in 2M K2CO3 (41 mmol) and EtOH (20 ml) and the reaction was stirred for 15 min. EtOH was then removed by rotary evaporation and the resulting aqueous layer was acidified with HCl (2M) to a pH of 2 and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous Na2SO4, filtered and evaporated by a rotary evaporator to give the crude product 1.1 g (52%). Finally, the crude product (1.1 g, 4.2 mmol), EDCI (1.20 g, 6.3 mmol), HOBt (851 mg, 6.3 mmol), DMAP (5 mg, 0.04 mmol) and TEA (18.9 mmol) were dissolved in MeCN (8 ml), and the resulting solution was heated to 140° C. in microwave for 10 min. The reaction mixture was cooled, poured into water, acidified with HCl (2M) to a pH of 2 and filtered. The filtrate was washed with 0.1 M NaOH solution and dried over anhydrous Na2SO4, filtered and evaporated by a rotary evaporator to give the product (676 mg, 66%).

1. temperaturecooled to room temperature
2. customTHF was removed by rotary evaporation
3. filtrationfiltered
4. washThe filter cake washed with 0.1M NaOH solution
5. customfinally dried
6. customto give the crude product 2.4 g (86%)
7. stirringthe reaction was stirred for 15 min
8. customEtOH was then removed by rotary evaporation
9. extractionextracted with ethyl acetate
10. washThe organic layer was washed with saturated brine
11. dry with materialdried over anhydrous Na2SO4
12. filtrationfiltered
13. customevaporated by a rotary evaporator
14. customto give the crude product 1.1 g (52%)
15. temperaturethe resulting solution was heated to 140° C. in microwave for 10 min
16. temperatureThe reaction mixture was cooled
17. filtrationfiltered
18. washThe filtrate was washed with 0.1 M NaOH solution
19. dry with materialdried over anhydrous Na2SO4
20. filtrationfiltered
21. customevaporated by a rotary evaporator

ORD record

ord-1d0cfa924c20469ba2abbb27f5701aa7

Source dataset

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08158623B2