1,2-Dibromoethane → 10-Bromo-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepine

HRID 575010Notes

Reaction equation

[Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([C:9]2[NH:10][CH:11]=[CH:12][N:13]=2)[CH:3]=1.Br[CH2:15][CH2:16]Br.C(=O)([O-])[O-].[K+].[K+].C([O-])([O-])=O.[Cs+].[Cs+]>CN(C)C=O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]2[O:8][CH2:16][CH2:15][N:10]3[C:9](=[N:13][CH:12]=[CH:11]3)[C:4]=2[CH:3]=1

Participants

Conditions

Temperature: 100 °C

Procedure

Into a 20 L 4-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen was placed a solution of 4-bromo-2-(1H-imidazol-2-yl)phenol (835 g, 3.49 mol, 1.00 equiv) in N,N-dimethylformamide (8.5 L), 1,2-dibromoethane (2366 g, 12.59 mol, 3.60 equiv), potassium carbonate (1930 g, 4.00 equiv), and Cs2CO3 (1160 g, 1.00 equiv). The resulting solution was stirred at 100° C. overnight, quenched by the addition of 20 L of water/ice and extracted with 4×10 L of ethyl acetate. The combined organic layers were washed with 4×5 L of brine, dried over anhydrous sodium sulfate and concentrated under vacuum. The crude product was re-crystallized from EA:PE (1:2) to afford 350 g (38%) of 9-Bromo-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene.

Workup

customInto a 20 L 4-necked round-bottom flask purged
temperaturemaintained with an inert atmosphere of nitrogen
customquenched by the addition of 20 L of water/ice
extractionextracted with 4×10 L of ethyl acetate
washThe combined organic layers were washed with 4×5 L of brine
dry with materialdried over anhydrous sodium sulfate
concentrationconcentrated under vacuum
customThe crude product was re-crystallized from EA

Sources & evidence

ORD record: ord-e8e73e80d615402d80221622cbbf22b4
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09034866B2

Reaction notes

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