Acetamide, N-(4-fluoro-3-nitrophenyl)- → N-{3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}acetamide

HRID 1435405Notes

Reaction equation

HRID 1435405 reaction equation
[NH2:1][CH2:2][CH:3]1[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1.F[C:10]1[CH:15]=[CH:14][C:13]([NH:16][C:17](=[O:19])[CH3:18])=[CH:12][C:11]=1[N+:20]([O-:22])=[O:21]>CCO>[N+:20]([C:11]1[CH:12]=[C:13]([NH:16][C:17](=[O:19])[CH3:18])[CH:14]=[CH:15][C:10]=1[NH:1][CH2:2][CH:3]1[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1)([O-:22])=[O:21]

Participants

4

Reactant 2

HCID 67694Acetamide, N-(4-fluoro-3-nitrophenyl)-HCID 27732104-Aminomethyltetrahydropyran

Product 1

HCID 57937362N-{3-Nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}acetamide

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

4-Aminomethyl tetrahydropyran (13.7 g, 0.119 mol) was added to a solution of N-(4-Fluoro-3-nitrophenyl)acetamide (20.2 g, 0.102 mol) and TEA (20.9 mL, 15.2 g, 0.15 mol) in EtOH (350 mL). The reaction mixture was stirred overnight at reflux. The orange-red solid was collected by filtration, washed with water and dried in vacuo. The filtrate was concentrated. The residue was dissolved in EtOAc, washed with H2O, brine and dried over anhydrous Na2SO4. The crude product was purified by silica gel flash chromatography using EtOAc as eluent. Total yield: 28.9 g (97%). 1H NMR (400 MHz, CHLOROFORM-D) δ 1.4 (m, 2 H), 1.7 (m, 2 H), 1.89-2.00 (m, 1 H), 2.18 (s, 3 H), 3.22 (dd, J=6.44, 5.66 Hz, 2 H), 3.42 (dt, J=11.86, 2.05 Hz, 2 H), 4.02 (dd, J=10.94, 3.71 Hz, 2 H), 6.84 (d, J=9.37 Hz, 1 H), 7.20 (br.s, 1 H), 7.81 (dd, J=9.37, 2.54 Hz, 1 H), 8.09 (d, J=2.54 Hz, 1 H), 8.10-8.12 (m, 1 H).

Workup

  1. temperatureat reflux
  2. filtrationThe orange-red solid was collected by filtration
  3. washwashed with water
  4. customdried in vacuo
  5. concentrationThe filtrate was concentrated
  6. dissolutionThe residue was dissolved in EtOAc
  7. washwashed with H2O, brine
  8. dry with materialdried over anhydrous Na2SO4
  9. customThe crude product was purified by silica gel flash chromatography

Sources & evidence

ORD record
ord-51cc8f4f0ef6492a8badc422aa5f0f25
Source dataset
uspto-grants-2009_11
Patent number
US07615642B2

Reaction notes

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