(E)-ethyl 3-(4-bromo-2-nitrophenyl)-2-(cyanomethyl)acrylate → ethyl 2-amino-8-bromo-3H-benzo[b]azepine-4-carboxylate

HRID 1689733Notes

Reaction equation

[Br:1][C:2]1[CH:7]=[CH:6][C:5](/[CH:8]=[C:9](\[CH2:15][C:16]#[N:17])/[C:10]([O:12][CH2:13][CH3:14])=[O:11])=[C:4]([N+:18]([O-])=O)[CH:3]=1>C(O)(=O)C.[Fe]>[NH2:17][C:16]1[CH2:15][C:9]([C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:8][C:5]2[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][C:4]=2[N:18]=1

Participants

Conditions

Temperature: 90 °C

Procedure

To a solution of (E)-ethyl 3-(4-bromo-2-nitrophenyl)-2-(cyanomethyl)acrylate (1.00 g, 2.9 mmol) in acetic acid (25 mL) was added iron powder (1.10 g, 19.0 mmol). The mixture was heated to 90° C. for 5 hours. Upon cooling the acetic acid was removed under vacuum and the resulting semisolid was dissolved in 50% K2CO3 (100 mL) and EtOAc (100 mL). The mixture was filtered to remove insoluble material and the phases were separated. The aqueous phase was extracted with EtOAc (2×100 mL). The combined organics were dried and concentrated. The concentrate was purified via flash chromatography (Biotage 40 m, 5% MeOH/CH2Cl2) to yield (1E,4E)-ethyl 2-amino-8-bromo-3H-benzo[b]azepine-4-carboxylate (0.52 g, 57%).

Workup

customwas removed under vacuum
dissolutionthe resulting semisolid was dissolved in 50% K2CO3 (100 mL)
filtrationThe mixture was filtered
customto remove insoluble material
customthe phases were separated
extractionThe aqueous phase was extracted with EtOAc (2×100 mL)
customThe combined organics were dried
concentrationconcentrated
customThe concentrate was purified via flash chromatography (Biotage 40 m, 5% MeOH/CH2Cl2)

Sources & evidence

ORD record: ord-942359f59c484f22970830688aaa6fc5
Source dataset: uspto-grants-2012_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08153622B2

Reaction notes

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