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

To a solution of the dihydrobenzazepine (270 mg, 0.70 mmol) from step F above in pyridine (15 mL) were added potassium carbonate (967 mg, 7.0 mmol) and p-toluenesulfonylhydrazide (672 mg, 3.5 mmol) in batches. The reaction solution was heated under reflux for 24 hours 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% methanol/dichloromethane) to give the desired 8-bromotetrahydrobenzazepine (176 mg, 65%): 1H NMR (500 MHz, CDCl3) δ 7.28 (d, J=2.1 Hz, 1H), 7.19 (dd, J=8.2, 1.7 Hz, 1H), 6.64 (d, J=8.2 Hz, 2H), 6.60-6.56 (m, 2H), 4.31 (t, J=4.4 Hz, 2H), 4.12 (d, J=9.9 Hz, 1H), 3.83 (br, 1H), 3.69 (d, J=14.2 Hz, 1H), 3.26 (t, J=4.4 Hz, 2H), 3.13-3.10 (m, 1H), 2.95-2.90 (m, 1H), 2.89 (s, 3H), 2.32 (s, 3H), 2.24-2.17 (m, 1H), 2.06-2.04 (m, 1H); ESI MS m/z 387, 389 [M+H]+.

1. temperatureThe reaction solution was heated
2. temperatureunder reflux for 24 hours
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% methanol/dichloromethane)

ORD record

ord-94e8e862d83a4d33ab7a97459ca247df

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09403776B2