Hydroxyamine hydrochloride → HCID 57941547, compound

To a solution of to 2-bromo-5a,7,8,9,10,10a-hexahydrocyclohepta[b]indol-6(5H)-one (1.5 g, 5.4 mmol) in ethanol (14 mL) was added solutions of hydroxylamine hydrochloride (750 mg, 11 mmol) in water (10 mL) and sodium acetate (1.46 g, 18 mmol) in water (10 mL). The reaction mixture was heated at reflux for 5 h, cooled and concentrated. The residue was diluted with ethyl acetate and washed with water (2×50 mL). The organic phase was dried over sodium sulfate, filtered and concentrated to a brown solid. The oxime was dissolved in THF (54 mL) and LAH (1.0 M in THF, 16.2 mL, 16.2 mmol) was added dropwise. The reaction was heated at reflux for 4 h and cooled in an ice bath. Methanol was added dropwise until bubbling ceased. The mixture was diluted with aqueous NaHSO3 and stirred vigorously for 15 min and extracted with ethyl acetate (2×150 mL). The extracts were combined, dried over sodium sulfate, filtered and concentrated. The crude amine was purified by flash chromatography on silica (2% to 5% methanol/methylene chloride gradient) to provide 2-bromo-5,5a,6,7,8,9,10,10a-octahydrocyclohepta[b]indol-6-amine as a brown oil. The oil was diluted in diethyl ether and HCl (1.0 M in diethyl ether) was added. The resulting precipitate was collected by filtration to provide 2-bromo-5,5a,6,7,8,9,10,10a-octahydrocyclohepta[b]indol-6-amine hydrochloride (980 mg, 57%). as a light brown solid. 1H-NMR (CD3OD): δ 7.65 (s, 1H), 7.28-7.21 (m, 2H), 4.68-4.66 (m, 1H), 3.08-3.01 (m, 1H), 2.84-2.76 (m, 1H), 2.33-2.25 (m, 1H), 2.15-1.93 (m, 4H), 1.65-1.55 (m, 1H); MS m/z (M−1) 277, 279.

1. temperatureThe reaction mixture was heated
2. temperatureat reflux for 5 h
3. temperaturecooled
4. concentrationconcentrated
5. additionThe residue was diluted with ethyl acetate
6. washwashed with water (2×50 mL)
7. dry with materialThe organic phase was dried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated to a brown solid
10. dissolutionThe oxime was dissolved in THF (54 mL)
11. temperatureThe reaction was heated
12. temperatureat reflux for 4 h
13. temperaturecooled in an ice bath
14. customuntil bubbling
15. additionThe mixture was diluted with aqueous NaHSO3
16. extractionextracted with ethyl acetate (2×150 mL)
17. dry with materialdried over sodium sulfate
18. filtrationfiltered
19. concentrationconcentrated
20. customThe crude amine was purified by flash chromatography on silica (2% to 5% methanol/methylene chloride gradient)

ORD record

ord-826fff50dcbe454e9cec5b52f2221953

Source dataset

uspto-grants-2009_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07622494B2