p-Fluoronitrobenzene → 1-Acetyl-4-(4-nitrophenyl)-1,4-diazepane

HRID 1713810Notes

Reaction equation

HRID 1713810 reaction equation
[C:1]([N:4]1[CH2:10][CH2:9][CH2:8][NH:7][CH2:6][CH2:5]1)(=[O:3])[CH3:2].CCN(C(C)C)C(C)C.F[C:21]1[CH:26]=[CH:25][C:24]([N+:27]([O-:29])=[O:28])=[CH:23][CH:22]=1>>[C:1]([N:4]1[CH2:10][CH2:9][CH2:8][N:7]([C:21]2[CH:26]=[CH:25][C:24]([N+:27]([O-:29])=[O:28])=[CH:23][CH:22]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2]

Participants

4

Reactant 3

HCID 9590p-FluoronitrobenzeneHCID 81531DiisopropylethylamineHCID 4186202N-Acetylhomopiperazine

Product 1

HCID 594642511-Acetyl-4-(4-nitrophenyl)-1,4-diazepaneYield 53%

Conditions

Temperature
80 °C

Procedure

N-Acetylhomopiperazine (7.2 mL, 54.6 mmol) and DIPEA (12.3 mL, 74.4 mmol) were added to a stirred solution of 4-fluoronitrobenzene (7.0 g, 49.6 mmol) acetonitrile (100 mL) and the mixture was heated to 80° C. under nitrogen with stirring for 16 h. Volatile material was removed by evaporation and the residue was dissolved in EtOAc (150 mL) and water (150 mL) was added. The organic layer was separated and the aqueous layer was extracted again with EtOAc (2×150 mL). The organic layers were combined and dried, concentrated by evaporation then the residue was triturated with isohexane to give the title compound (5.6 g, 53%) as a solid; 1H NMR δ 8.01 (2H, qd), 6.92-6.82 (2H, m), 3.80 (1H, t), 3.70-3.56 (5H, m), 3.35 (2H, dt), 1.97-1.71 (5H, m); MS m/e MH+: 264.

Workup

  1. customVolatile material was removed by evaporation
  2. dissolutionthe residue was dissolved in EtOAc (150 mL)
  3. additionwater (150 mL) was added
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted again with EtOAc (2×150 mL)
  6. customdried
  7. concentrationconcentrated by evaporation
  8. customthe residue was triturated with isohexane

Sources & evidence

ORD record
ord-147939cd0da54ea89feca37680803700
Source dataset
uspto-grants-2010_09
Patent number
US07795283B2

Reaction notes

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