4-Chlorophenol → 2-(4-Chlorophenoxy)-1,3-difluoro-5-nitrobenzene

HRID 1669985Notes

Reaction equation

HRID 1669985 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([N+:10]([O-:12])=[O:11])[CH:5]=[C:6]([F:9])[C:7]=1F.[Cl:13][C:14]1[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][CH:15]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[Cl:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][C:7]2[C:6]([F:9])=[CH:5][C:4]([N+:10]([O-:12])=[O:11])=[CH:3][C:2]=2[F:1])=[CH:16][CH:15]=1

Participants

5

Reactant 3

HCID 46844-ChlorophenolHCID 10796Cesium carbonateHCID 27827931,2,3-Trifluoro-5-nitrobenzene

Product 1

HCID 469415962-(4-Chlorophenoxy)-1,3-difluoro-5-nitrobenzeneYield 106.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 3,4,5-trifluoronitrobenzene (6.6 g, 37 mmol), dry DMF (30 ml), 4-chlorophenol (5.26 g, 41 mmol), and Cs2CO3 (18.8 g, 58 mmol) was stirred under N2 at 60-70 C for 1-2 hrs. After cooling to room temperature, the reaction mixture was partitioned between H2O and EtOAc. The phases were separated and the aqueous phase was further extracted with EtOAc (2×). The EtOAc extractions were washed with sat'd NaCl (1×), dried over Na2SO4, and concentrated in vacuo to give 4-(4-chlorophenoxy)-3,5-difluoronitrobenzene (11.3 g, 106%) which was used in the next step without further purification. 1H NMR (CDCl3): δ 6.90 (d, 2H, J=7.6 Hz), 7.28 (d, 2H, J=7.6 Hz), 7.94 (d, 2H, J=6.4 Hz). Note: K2CO3/acetonitrile can be used in lieu of Cs2CO3/DMF.

Workup

  1. customthe reaction mixture was partitioned between H2O and EtOAc
  2. customThe phases were separated
  3. extractionthe aqueous phase was further extracted with EtOAc (2×)
  4. extractionThe EtOAc extractions
  5. washwere washed with sat'd NaCl (1×)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8d48ee49d6bc4d09b099b08b41a72e0b
Source dataset
uspto-grants-2011_08
Patent number
US07989661B2

Reaction notes

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