Propylene Oxide → 10-Bromo-6-methyl-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine
Reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5](F)=[C:6]([C:8]2[NH:9][CH:10]=[CH:11][N:12]=2)[CH:7]=1.[H-].[Na+].[CH2:16]1[O:19][CH:17]1[CH3:18]>CN(C)C=O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[O:19][CH:17]([CH3:18])[CH2:16][N:9]3[CH:10]=[CH:11][N:12]=[C:8]3[C:6]=2[CH:7]=1Participants
Procedure
To a solution of 2-(5-bromo-2-fluoro-phenyl)-1H-imidazole (250 mg, 1.0371 mmol) in dimethylformamide (3.0 mL) was added sodium hydride (1.1 equiv., 45.6 mg, 1.1408 mmol) at 0° C. The reaction was stirred at this temperature for 10 minutes, then (+/−)-propylene oxide (1.2 equiv., 0.09 mL, 1.2445 mmol) was added and the mixture was allowed to warm up to room temperature. The reaction was then heated to 95° C. for 6 h. The reaction mixture was cooled to room temperature and quenched with saturated aqueous ammonium chloride. The solution was extracted 3× with methylene chloride. The organic layers were combined, dried with sodium sulfate, and concentrated in vacuo. The crude was purified by flash chromatography (5-100% EtOAc in heptanes) to afford 188 mg (65% yield) of an orange solid.
Workup
- temperatureThe reaction was then heated to 95° C. for 6 h
- temperatureThe reaction mixture was cooled to room temperature
- customquenched with saturated aqueous ammonium chloride
- extractionThe solution was extracted 3× with methylene chloride
- dry with materialdried with sodium sulfate
- concentrationconcentrated in vacuo
- customThe crude was purified by flash chromatography (5-100% EtOAc in heptanes)
Sources & evidence
- ORD record
- ord-14f28005a85546bcae9e08ca2230b548
- Source dataset
- uspto-grants-2015_05
- Patent number
- US09034866B2
Reaction notes
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