Pyridine → 8-Bromo-2,3,4,5-tetrahydro-1H-benzo[b]azepine

To a solution of the dihydrobenzazepine (2.43 g, 7.31 mmol) from step F above in pyridine (50 mL) were added potassium carbonate (8.08 g, 58.5 mmol) and p-toluenesulfonylhydrazide (5.45 g, 29.3 mmol) in batches. The reaction solution was heated under reflux for 48 h and then cooled to room temperature. The resultant reaction mixture was filtered through Celite. The Celite bed was washed with ethyl acetate. The filtrate was concentrated under reduced pressure. The residue dissolved in ethyl acetate was washed with water and brine, dried over sodium sulfate and concentrated under reduced pressure. The residue obtained was purified by flash column chromatography (3 to 5% methanol/dichloromethane) to give the desired 8-bromotetrahydrobenzazepine (1.74 g, 71%): 1H NMR (500 MHz, CDCl3) δ 7.31 (d, J=2.1 Hz, 1H), 7.20-7.16 (m, 1H), 7.13-7.10 (m, 2H), 7.04 (t, J=8.6 Hz, 2H), 6.49 (br, 1H), 4.24 (d, J=9.3 Hz, 1H), 3.88 (d, J=12.2 Hz, 1H), 3.67 (d, J=14.3 Hz, 1H), 3.12-3.09 (m, 1H), 2.98-2.93 (m, 1H), 2.34 (s, 3H), 2.30-2.23 (m, 1H), 2.08-2.04 (m, 1H); ESI MS m/z 334, 336 [M+H]+.

1. temperatureThe reaction solution was heated
2. temperatureunder reflux for 48 h
3. customThe resultant reaction mixture
4. filtrationwas filtered through Celite
5. washThe Celite bed was washed with ethyl acetate
6. concentrationThe filtrate was concentrated under reduced pressure
7. dissolutionThe residue dissolved in ethyl acetate
8. washwas washed with water and brine
9. dry with materialdried over sodium sulfate
10. concentrationconcentrated under reduced pressure
11. customThe residue obtained
12. customwas purified by flash column chromatography (3 to 5% methanol/dichloromethane)

ORD record

ord-e9509eafefe24449b0cd2bf637cc003e

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08791101B2