4-Fluorophenol → 4-(4-Fluorophenoxy)-3,5-difluoronitrobenzene

HRID 1669983Notes

Reaction equation

HRID 1669983 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.[F: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>[F: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 97324-FluorophenolHCID 10796Cesium carbonateHCID 27827931,2,3-Trifluoro-5-nitrobenzene

Product 1

HCID 575886774-(4-Fluorophenoxy)-3,5-difluoronitrobenzeneYield 105%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 3,4,5-trifluoronitrobenzene (20.0 g, 113 mmol, commercially available from AsymChem of Durham, N.C.), dry DMF (100 ml), 4-fluorophenol (13.9 g, 124 mmol), and Cs2CO3 (56 g, 172 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-fluorophenoxy)-3,5-difluoronitrobenzene (32.0 g, 105%) which was used in the next step without further purification. 1H NMR (DMSO-d6): δ7.15 (m, 2H), 7.22 (m, 2H), 8.31 (d, 2H, J=7.6 Hz).

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-639bd02232354d9cb9861964b22bd8f7
Source dataset
uspto-grants-2011_08
Patent number
US07989661B2

Reaction notes

Loading…