Hydrochloric Acid → Ethyl (2,5-difluoro-4-nitrophenyl)carbamate

HRID 2258619Notes

Reaction equation

HRID 2258619 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:10]=[C:9]([N+:11]([O-:13])=[O:12])[C:8]([F:14])=[CH:7][C:5]=1[NH2:6].[H][H].Cl[C:18]([O:20][CH2:21][CH3:22])=[O:19].Cl.[OH-].[Na+]>CN(C)C=O.O>[CH2:21]([O:20][C:18]([NH:6][C:5]1[CH:7]=[C:8]([F:14])[C:9]([N+:11]([O-:13])=[O:12])=[CH:10][C:4]=1[F:3])=[O:19])[CH3:22]

Participants

9

Reactant 6

HCID 313Hydrochloric Acid2×HCID 10928Ethyl chloroformateHCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 2359302,5-Difluoro-4-nitroanilineHCID 178418361HCID 178418361, compound

Product 1

HCID 22921575Ethyl (2,5-difluoro-4-nitrophenyl)carbamateYield 61.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent2×

Procedure

Under a nitrogen atmosphere, a stirred mixture of 2.2 grams (0.055 mole) of sodium hydride (60% in mineral oil) in about 40 mL of N,N-dimethylformamide was cooled in an ice-bath, and a solution of 8.0 grams (0.046 mole) of 2,5-difluoro-4-nitroaniline in 100 mL of N,N-dimethylformamide was added dropwise. After the evolution of hydrogen ceased, 7.5 grams (0.069 mole) of ethyl chloroformate was added in small portions. Upon completion of the addition, the reaction mixture was allowed to warm to ambient temperature, where it stirred for about 20 hours. After this time, the reaction mixture was poured into aqueous 3N hydrochloric acid and ice. The resultant precipitate was collected by filtration and dissolved in ethanol. To this stirred solution was then added dropwise a solution of 3.3 grams (0.083 mole) of sodium hydroxide dissolved in a minimum of water. Upon completion of the addition, the reaction mixture was stirred at ambient temperature for about 25 minutes and then made acidic with concentrated hydrochloric acid. The reaction mixture was poured into water, and the resultant solid was collected by filtration. The solid was dried, yielding 7.0 grams of N-ethoxycarbonyl-2,5-difluoro-4-nitroaniline. The NMR spectrum was consistent with the proposed structure.

Workup

  1. temperaturewas cooled in an ice-bath
  2. additionUpon completion of the addition
  3. filtrationThe resultant precipitate was collected by filtration
  4. dissolutiondissolved in ethanol
  5. additionUpon completion of the addition
  6. stirringthe reaction mixture was stirred at ambient temperature for about 25 minutes
  7. filtrationthe resultant solid was collected by filtration
  8. customThe solid was dried

Sources & evidence

ORD record
ord-d20d1606a21f442e9b27ee2849f7e535
Source dataset
uspto-grants-1997_08
Patent number
US05661108

Reaction notes

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