Triethylamine → 2,4-difluoro-5-nitro-N-phenylaniline

HRID 1241932Notes

Reaction equation

HRID 1241932 reaction equation
[F:1][C:2]1[CH:8]=[C:7]([F:9])[C:6]([N+:10]([O-:12])=[O:11])=[CH:5][C:3]=1[NH2:4].[C:13]1(B(O)O)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C(N(CC)CC)C>ClCCl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[F:1][C:2]1[CH:8]=[C:7]([F:9])[C:6]([N+:10]([O-:12])=[O:11])=[CH:5][C:3]=1[NH:4][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

6

Reactant 3

HCID 8471Triethylamine2×HCID 66827Phenylboronic Acid2×HCID 27583122,4-Difluoro-5-nitroaniline

Product 1

HCID 219378022,4-difluoro-5-nitro-N-phenylanilineYield 91%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalyst2×HCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 2,4-difluoro-5-nitroaniline (3.00 g, 17.23 mmol) (see EP0379894 A3), phenylboronic acid (6.30 g, 51.69 mmol), copper(II) acetate (3.13 g, 17.23 mmol) and 4 Å molecular sieves (3.0 g) in dichloromethane (170.0 mL) and triethylamine (12.01 mL, 43.08 mmol) was placed in a round bottomed flask. The resulting suspension was stirred under at room temperature under a dry ambient atmosphere 50 h. The mixture was filtered through diatomaceous earth and the solvent was evaporated. Additional phenylboronic acid (6.30 g, 51.69 mmol), copper(II) acetate (3.13 g, 17.23 mmol), molecular sieves (3.00 g) triethylamine (12.01 mL, 43.08 mmol), and dichloromethane (170.00 mL) were added and the slurry was stirred for 12 h. The mixture was again filtered through diatomaceous earth and the solvent was evaporated. The resulting residue was re-dissolved in EtOAc, adsorbed on silica and flash chromatographed (15% EtOAc/hexanes) to give 2,4-difluoro-5-nitro-N-phenylaniline as an orange solid (3.92 g, 91% yield).

Workup

  1. filtrationThe mixture was filtered through diatomaceous earth
  2. customthe solvent was evaporated
  3. stirringthe slurry was stirred for 12 h
  4. filtrationThe mixture was again filtered through diatomaceous earth
  5. customthe solvent was evaporated
  6. dissolutionThe resulting residue was re-dissolved in EtOAc
  7. customchromatographed (15% EtOAc/hexanes)

Sources & evidence

ORD record
ord-7083e62085a346958708e0d3195792c0
Source dataset
uspto-grants-2006_10
Patent number
US07115644B2

Reaction notes

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