Acetamide, N-(4-fluoro-3-nitrophenyl)- → N-(4-{[(4,4-Difluorocyclohexyl)methyl]amino}-3-nitrophenyl)acetamide

HRID 1435487Notes

Reaction equation

HRID 1435487 reaction equation
F[C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:11])[CH3:10])=[CH:4][C:3]=1[N+:12]([O-:14])=[O:13].Cl.[F:16][C:17]1([F:25])[CH2:22][CH2:21][CH:20]([CH2:23][NH2:24])[CH2:19][CH2:18]1>CCO>[F:16][C:17]1([F:25])[CH2:22][CH2:21][CH:20]([CH2:23][NH:24][C:2]2[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:11])[CH3:10])=[CH:4][C:3]=2[N+:12]([O-:14])=[O:13])[CH2:19][CH2:18]1

Participants

4

Reactant 2

HCID 67694Acetamide, N-(4-fluoro-3-nitrophenyl)-HCID 451589311-(4,4-Difluorocyclohexyl)methanamine hydrochloride

Product 1

HCID 57441084N-(4-{[(4,4-Difluorocyclohexyl)methyl]amino}-3-nitrophenyl)acetamide

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

N-(4-Fluoro-3-nitrophenyl)acetamide (1.15 g, 5.84 mmol) and [(4,4-difluorocyclohexyl)methyl]amine hydrochloride (1.30 g, 7.59 mmol) were stirred in 30 mL of EtOH containing TEA (2.40 mL, 17.5 mmol) at 80° C. for 48 h. The solvent was evaporated. The residue was dissolved in EtOAc and washed with aqueous 5% KHSO4 solution, saturated aqueous NaHCO3 solution, saturated aqueous NaCl solution and dried over anhydrous Na2SO4. The product was crystallized from EtOAc. The left over mother liquor was purified by flash chromatography on silica gel using hexane/acetone (2:1) as eluent. Yield: 1.50 g (78%); 1H NMR (400 MHz, CDCl3) δ 1.33-1.47 (m, 2 H), 1.66-1.77 (m, 2 H), 1.77-1.86 (m, 1 H), 1.89-1.93 (m, 1 H), 1.93-1.97 (m, 1 H), 2.10-2.17 (m, 2 H), 2.18 (s, 3 H), 3.23 (dd, J=6.74, 5.76 Hz, 2 H), 6.83 (d, J=9.37 Hz, 1 H), 7.15 (s, 1 H), 7.80 (dd, J=9.18, 2.54 Hz, 1 H), 8.09 (d, J=2.54 Hz, 2 H).

Workup

  1. customThe solvent was evaporated
  2. dissolutionThe residue was dissolved in EtOAc
  3. washwashed with aqueous 5% KHSO4 solution, saturated aqueous NaHCO3 solution, saturated aqueous NaCl solution
  4. dry with materialdried over anhydrous Na2SO4
  5. customThe product was crystallized from EtOAc
  6. waitThe left over mother liquor
  7. customwas purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-816fd2d794ce41e4baa339af6fa5bdfc
Source dataset
uspto-grants-2009_11
Patent number
US07615642B2

Reaction notes

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