Ethanol → Methyl 4-bromo-12-oxo-5,6,7,8,9,10,11,12-octahydrocycloocta[b]quinoline-1-carboxylate

Temperature

130 °C

A mixture of methyl 2-oxocyclooctanecarboxylate (32.0 g, 174 mmol), methyl 3-amino-4-bromobenzoate (20.0 g, 87 mmol) and ethanol (120 mL) was heated to reflux, at an oil bath of 130° C., acetic acid (1.5 mL) was added and the mixture was reflux for 1.5 hours. Hot PPA (200 g, 120° C.) was added to the reaction mixture carefully. The reaction mixture was heated at an oil bath of 130° C. for 3 hours. After cooling for a while, ice (200 g), ethyl acetate (60 mL) and petroleum ether (60 mL) were added to the reaction mixture, the mixture was concentrated until 200 mL solvent was removed. Then water (600 mL) and ethyl acetate (60 mL) were added, the resulting mixture was stayed at room temperature overnight. A light brown solid was slowly formed. The mixture was filtered and the filtered cake was dried to give a light brown solid, which was placed into methanol (90 mL). SOCl2 (30 mL) was added dropwise with cooling with an ice-bath. The resulting mixture was heated to reflux for 4 hours, concentrated and treated with saturated NaHCO3 solution (60 mL) and ethyl acetate (30 mL), filtered and the filtered cake was dried to give desired product (6.6 g) as a pale white solid (21%). 1H NMR (DMSO-d6) δ10.25 (s, 1H), 7.96-7.98 (d, 1H, J=7.6 Hz), 7.09-7.11 (d, 1H, J=7.6 Hz), 3.02-3.06 (m, 2H), 2.63-2.66 (m, 2H), 1.75-1.77 (m, 2H), 1.53-1.55 (m, 2H), and 1.36-1.39 (m, 4H). MS (ESI) m/e [M+1]+ 364/366.

1. temperaturewas heated
2. temperaturethe mixture was reflux for 1.5 hours
3. additionHot PPA (200 g, 120° C.) was added to the reaction mixture carefully
4. temperatureThe reaction mixture was heated at an oil bath of 130° C. for 3 hours
5. additionwere added to the reaction mixture
6. concentrationthe mixture was concentrated until 200 mL solvent
7. customwas removed
8. additionThen water (600 mL) and ethyl acetate (60 mL) were added
9. customA light brown solid was slowly formed
10. filtrationThe mixture was filtered
11. customthe filtered cake was dried
12. customto give a light brown solid, which
13. temperaturewith cooling with an ice-bath
14. temperatureThe resulting mixture was heated
15. temperatureto reflux for 4 hours
16. concentrationconcentrated
17. additiontreated with saturated NaHCO3 solution (60 mL) and ethyl acetate (30 mL)
18. filtrationfiltered
19. customthe filtered cake was dried

ORD record

ord-2290a493b38f41868f82b4638c0cb98c

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09328111B2