Ammonia → HCID 58494950, compound

To a solution of 22.5 g of 6-chloro-1H-3-benzazepine-2,4(3H,5H)-dione in 200 ml of THF were added dropwise 38 ml of a 10 M borane-dimethyl sulfide complex at 0° C. for 20 minutes, followed by stirring for 2.5 hours. The reaction mixture was heated and refluxed, and further stirred. To the reaction mixture was added dropwise 30 ml of MeOH under ice-cooling, followed by stirring, and then 30 ml of 4 M hydrochloric acid was added dropwise thereto, followed by heating and refluxing for 1 hour after generation of bubbles substantially settled. The mixture was alkalified by the addition of aqueous ammonia and a 1 M aqueous sodium hydroxide solution, followed by extraction with chloroform. The organic layer was dried over anhydrous sodium sulfate and then filtered. The filtrate was concentrated under reduced pressure, the residue was dissolved in EtOH, and activated carbon was added thereto, followed by heating and refluxing, and then filtering on amino silica gel, and the filtrate was concentrated under reduced pressure. To a solution of 18.7 g of the resulting residue in 180 ml of dichloromethane was added 17 ml of pyridine, followed by ice-cooling, and 13 ml of ethyl chlorocarbonate was added dropwise thereto, followed by stirring for 1.5 hours. The reaction mixture was concentrated under reduced pressure, the residue was diluted with EtOAc, then washed with 1 M hydrochloric acid and water, dried over anhydrous sodium sulfate, and then filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography (elution solvent: HEX-EtOAc) to obtain 9.653 g of ethyl 6-chloro-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylate as a reddish brown oily substance.

1. temperatureThe reaction mixture was heated
2. temperaturerefluxed
3. temperaturecooling
4. stirringby stirring
5. temperatureby heating
6. temperaturerefluxing for 1 hour after generation of bubbles
7. extractiona 1 M aqueous sodium hydroxide solution, followed by extraction with chloroform
8. dry with materialThe organic layer was dried over anhydrous sodium sulfate
9. filtrationfiltered
10. concentrationThe filtrate was concentrated under reduced pressure
11. dissolutionthe residue was dissolved in EtOH
12. additionactivated carbon was added
13. temperatureby heating
14. temperaturerefluxing
15. filtrationfiltering on amino silica gel
16. concentrationthe filtrate was concentrated under reduced pressure
17. additionTo a solution of 18.7 g of the resulting residue in 180 ml of dichloromethane was added 17 ml of pyridine
18. temperaturecooling
19. addition13 ml of ethyl chlorocarbonate was added dropwise
20. stirringby stirring for 1.5 hours
21. concentrationThe reaction mixture was concentrated under reduced pressure
22. additionthe residue was diluted with EtOAc
23. washwashed with 1 M hydrochloric acid and water
24. dry with materialdried over anhydrous sodium sulfate
25. filtrationfiltered
26. concentrationthe filtrate was concentrated under reduced pressure
27. customThe residue was purified by silica gel chromatography (elution solvent: HEX-EtOAc)

ORD record

ord-d586e41c30d24d97b5180686387ed6f7

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09108977B2