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

HRID 1598005Notes

Reaction equation

[NH:1]1[CH2:7][CH2:6][CH2:5][CH2:4][C:3]2[CH:8]=[CH:9][CH:10]=[CH:11][C:2]1=2.[Br:12]Br.[OH-].[K+]>OS(O)(=O)=O.S([O-])([O-])(=O)=O.[Ag+2]>[Br:12][C:10]1[CH:9]=[CH:8][C:3]2[CH2:4][CH2:5][CH2:6][CH2:7][NH:1][C:2]=2[CH:11]=1

Participants

Conditions

Temperature: 20 °C

Procedure

To 2,3,4,5-tetrahydro-1H-benzo[b]azepine (410 mg, 2.78 mmol; from Preparation 41) in conc. H2SO4 (5 mL) was added Ag2 SO4 (438 mg, 1.41 mmol). The mixture was stirred until the silver sulfate had dissolved and then Br2(l) (145 μL, 2.80 mmol) was added at 0°-5° C. over 15 minutes. The mixture was stirred in the dark and allowed to warm to 20° C. After 4 hours the mixture was poured into ice/H2O (50 mL), the pH was adjusted to 12-14 by the careful addition of 6N KOH with cooling, and then filtered through a pad of Celite. The pad was washed with CH3CN, CHCl3, and Et2 O. The aqueous phase was extracted with EtOAc and the organic extracts and washes were combined, dried over MgSO4(s), filtered and concentrated in vacuo to afford 468 mg of a waxy yellow solid. The 6-bromo (48 mg) and 8-bromo isomers (492 mg; GC-MS: 226, 228 (M+)) were separated by flash chromatography on silica (10% EtOAc/hexanes) and/or recrystallization (Et2O/Hexanes).

Workup

dissolutionhad dissolved
temperaturewith cooling
filtrationfiltered through a pad of Celite
washThe pad was washed with CH3CN, CHCl3, and Et2 O
extractionThe aqueous phase was extracted with EtOAc
dry with materialdried over MgSO4(s)
filtrationfiltered
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-e5c17ff4ea0b4f20ba04fbe45c6989fe
Source dataset: uspto-grants-1998_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05736534

Reaction notes

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