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

HRID 343152Notes

Reaction equation

HRID 343152 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 45.4%

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, prepared as in Part A, (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 is cooled to ambient temperature, filtered and washed with 2:1 water/ethanol. The wet solid is dissolved in methylene chloride, dried over anhydrous sodium sulfate, and evaporated in vacuo. The residue is triturated with hexane, filtered and washed with hexane. The product is dried under high vacuum to provide 9.32 g of 2-(4-Fluoro-2-nitro-phenylamino)-N-isopropyl-N-(4-methoxy-phenyl)-acetamide as an orange solid: 1H NMR (300 MHz, CDCl3) δ7.89 (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 is dissolved in methylene chloride
  6. dry with materialdried over anhydrous sodium sulfate
  7. customevaporated in vacuo
  8. customThe residue is triturated with hexane
  9. filtrationfiltered
  10. washwashed with hexane
  11. customThe product is dried under high vacuum

Sources & evidence

ORD record
ord-d7c3f30335f546caae5ef9e9c9ada4f1
Source dataset
uspto-grants-1999_01
Patent number
US05859007

Reaction notes

Loading…