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

HRID 230711Notes

Reaction equation

HRID 230711 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 48h. 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 silica gel flash chromatography using 2:1/hexanes:acetone as eluent. Yield: 1.50 g (78%). 1H NMR (400 MHz, CHLOROFORM-D) δ 1.33-1.47 (m, 2H), 1.66-1.77 (m, 2H), 1.77-1.86 (m, 1H), 1.89-1.93 (m, 1H), 1.93-1.97 (m, 1H), 2.10-2.17 (m, 2H), 2.18 (s, 3H), 3.23 (dd, J=6.74, 5.76 Hz, 2H), 6.83 (d, J=9.37 Hz, 1H), 7.15 (s, 1H), 7.80 (dd, J=9.18, 2.54 Hz, 1H), 8.09 (d, J=2.54 Hz, 2H).

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 silica gel flash chromatography

Sources & evidence

ORD record
ord-d8bf3163de764a21b830b9358ec428b6
Source dataset
uspto-grants-2009_07
Patent number
US07566788B2

Reaction notes

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