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

HRID 1040751Notes

Reaction equation

HRID 1040751 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-264a80f7505544c587631b4489201d7d
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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