Triethylamine → 1-Benzoyl-4-bromo-1,2,3,4-tetrahydro-benzo[b]azepin-5-one

1-Benzoyl-1,2,3,4-tetrahydro-benzo[b]azepin-5-one from Example E5.6 (54.2 g, 205 mmol), N-bromosuccinimide (3.6 g, 20.4 mmol) and bromine (11.1 ml, 214.7 mmol) were dissolved in dichloromethane (1.0 liter). Triethylamine (30 ml, 215 mmol) was added dropwise over 30 minutes then the reaction mixture was heated at reflux for 4 h. Additional bromine (1.1 ml, 21.5 mmol) and triethylamine (3.0 ml, 21.5 mmol) were added and the reaction mixture was heated at reflux for a further 4 h. Additional bromine (1.1 ml, 21.5 mmol) and triethylamine (3.0 ml, 21.5 mmol) were added again and the reaction mixture was heated at reflux for a further 4 h. On cooling to room temperature, the reaction solution was washed with 5% aqueous sodium metabisulfate solution (150 ml) and the aqueous phase was diluted with water (600 ml). The organic phase was separated, washed with saturated Na—HCO3 (aq), dried over sodium sulphate and filtered. The filtrate was diluted with EtOAc (100 ml), filtered through a silica pad (eluant; CH2Cl2) and reduced in vacuo to yield the title compound (73.6 g) which was used without further purification.

1. temperaturethe reaction mixture was heated
2. temperatureat reflux for 4 h
3. temperaturethe reaction mixture was heated
4. temperatureat reflux for a further 4 h
5. temperaturethe reaction mixture was heated
6. temperatureat reflux for a further 4 h
7. washthe reaction solution was washed with 5% aqueous sodium metabisulfate solution (150 ml)
8. additionthe aqueous phase was diluted with water (600 ml)
9. customThe organic phase was separated
10. washwashed with saturated Na—HCO3 (aq)
11. dry with materialdried over sodium sulphate
12. filtrationfiltered
13. additionThe filtrate was diluted with EtOAc (100 ml)
14. filtrationfiltered through a silica pad (eluant; CH2Cl2)

ORD-Eintrag

ord-78ed8321a43e4eb6864ea7b72d68c51a

Quelldatensatz

uspto-grants-2012_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08202858B2