Potassium Iodide → 2-(7-Methoxy-8-nitro-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl)-N,N-dimethyl-acetamide

HRID 1687059Notes

Reaction equation

HRID 1687059 reaction equation
[CH3:1][O:2][C:3]1[C:13]([N+:14]([O-:16])=[O:15])=[CH:12][C:6]2[CH2:7][CH2:8][NH:9][CH2:10][CH2:11][C:5]=2[CH:4]=1.Cl[CH2:18][C:19]([N:21]([CH3:23])[CH3:22])=[O:20].[I-].[K+].C(=O)([O-])[O-].[Cs+].[Cs+]>C(#N)C>[CH3:1][O:2][C:3]1[C:13]([N+:14]([O-:16])=[O:15])=[CH:12][C:6]2[CH2:7][CH2:8][N:9]([CH2:18][C:19]([N:21]([CH3:23])[CH3:22])=[O:20])[CH2:10][CH2:11][C:5]=2[CH:4]=1

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 10796Cesium carbonateHCID 758862-chloro-N,N-dimethylacetamideHCID 672643517-Methoxy-8-nitro-2,3,4,5-tetrahydro-1H-benzo[d]azepine

Product 1

HCID 672637882-(7-Methoxy-8-nitro-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl)-N,N-dimethyl-acetamideYield 79.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Into a 1-neck round-bottom flask was added 7-methoxy-8-nitro-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.5 g, 2.20 mmol), 2-chloro-N,N-dimethyl-acetamide (0.45 mL, 4.41 mmol), potassium iodide (0.18 g, 1.10 mmol), and cesium carbonate (2.16 g, 6.61 mmol), in acetonitrile (15 mL), and the reaction was stirred overnight at reflux. The reaction mixture was next partitioned between water and ethyl acetate, and the layers separated. The aqueous phase was extracted twice with ethyl acetate and the combined organic extracts were washed with water, dried (MgSO4), filtered, and concentrated, and the product was isolated by flash chromatography on SiO2 (MeOH/dichloromethane 0-10%) to give 2-(7-Methoxy-8-nitro-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl)-N,N-dimethyl-acetamide (537 mg, 79%) as a yellow solid. 1H-NMR (CDCl3) δ 7.67 (s, 1H), 6.82 (s, 1H), 3.95 (s, 3H), 3.30 (s, 2H), 3.09 (s, 3H), 2.98 (s, 3H), 2.85-3.05 (m, 4H), 2.73 (t, J=10.2 Hz, 4H); LC/MS (ESI+): 308.55 (M+H).

Workup

  1. temperatureat reflux
  2. customThe reaction mixture was next partitioned between water and ethyl acetate
  3. customthe layers separated
  4. extractionThe aqueous phase was extracted twice with ethyl acetate
  5. washthe combined organic extracts were washed with water
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customthe product was isolated by flash chromatography on SiO2 (MeOH/dichloromethane 0-10%)

Sources & evidence

ORD record
ord-215257b8169345d7a73e8ef2ba9cc7b3
Source dataset
uspto-grants-2012_04
Patent number
US08148391B2

Reaction notes

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