2,5-Difluoronitrobenzene → 2-(4-Fluoro-2-nitrophenylamino)-N-isopropyl-N-(4-methoxy-phenyl)-acetamide

HRID 1599094Notes

Reaction equation

HRID 1599094 reaction equation
F[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[N+:9]([O-:11])=[O:10].[NH2:12][CH2:13][C:14]([N:16]([CH:25]([CH3:27])[CH3:26])[C:17]1[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=1)=[O:15]>C(O)C.O>[F:8][C:5]1[CH:6]=[CH:7][C:2]([NH:12][CH2:13][C:14]([N:16]([CH:25]([CH3:27])[CH3:26])[C:17]2[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=2)=[O:15])=[C:3]([N+:9]([O-:11])=[O:10])[CH:4]=1

Participants

4

Reactant 2

HCID 677672,5-DifluoronitrobenzeneHCID 54496521N1-Isopropyl-N1-(4-methoxyphenyl)glycinamide

Product 1

HCID 540942822-(4-Fluoro-2-nitrophenylamino)-N-isopropyl-N-(4-methoxy-phenyl)-acetamideYield 43%

Reagents, catalysts & solvents 1

HCID 19096565Water ethanolSolvent

Procedure

A mixture of 9.06 g of 2,5-difluoro-nitrobenzene (60 mmol) and 12.64 g of 2-amino-N-isopropyl-N-(4-methoxy-phenyl)-acetamide (60 mmol, 1.0 equiv) were combined in 225 mL of 2:1 ethanol/water and heated to reflux under nitrogen and stirred vigorously overnight (approx. 16 hrs.). The resulting slurry was cooled to ambient temperature, filtered and washed with 2:1 water/ethanol. The wet solid was dissolved in methylene chloride, dried over anhydrous sodium sulfate, and evaporated in vacuo. The residue was triturated with hexane, filtered and washed with hexane. The product was dried under high vacuum to provide 9.32 g of the title compound as an orange solid. 1H NMR (300 MHz, CDCl3) d 7.89 (dd, 1H, J=3.1, 9.3), 7.12 (m, 3H), 6.99 (m, 2H), 6.35 (dd, 1H, J=4.8, 9.2), 5.03 (m, 1H), 3.89 (s, 3H), 3.57 (s, 2H), 1.09 (d, 6H, J=6.8); low resolution MS (ESI)m/e 362 (MH+).

Workup

  1. temperatureheated
  2. temperatureto reflux under nitrogen
  3. filtrationfiltered
  4. washwashed with 2:1 water/ethanol
  5. dissolutionThe wet solid was dissolved in methylene chloride
  6. dry with materialdried over anhydrous sodium sulfate
  7. customevaporated in vacuo
  8. customThe residue was triturated with hexane
  9. filtrationfiltered
  10. washwashed with hexane
  11. customThe product was dried under high vacuum

Sources & evidence

ORD record
ord-b629070a269b4975a999683bb7bd8b98
Source dataset
uspto-grants-1998_04
Patent number
US05739129

Reaction notes

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