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

Participants

Reaction Conditions

Reaction Steps

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).

Provenance & Evidence