4-Fluoroiodobenzene → 1-fluoro-4-[2-(4-fluorophenyl)ethynyl]benzene

HRID 1955295Notes

Reaction equation

HRID 1955295 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([F:9])=[CH:5][CH:4]=1)#[CH:2].[F:10][C:11]1[CH:16]=[CH:15][C:14](I)=[CH:13][CH:12]=1>C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)CC)C>[F:9][C:6]1[CH:7]=[CH:8][C:3]([C:1]#[C:2][C:14]2[CH:15]=[CH:16][C:11]([F:10])=[CH:12][CH:13]=2)=[CH:4][CH:5]=1

Participants

5

Reactant 2

HCID 96054-FluoroiodobenzeneHCID 5226271-Ethynyl-4-fluorobenzene

Product 1

HCID 52405331-fluoro-4-[2-(4-fluorophenyl)ethynyl]benzeneYield 93.7%

Reagents, catalysts & solvents 2

HCID 11776TriphenylphosphineCatalystHCID 8471TriethylamineSolvent

Procedure

A 2-Liter 4-neck round-bottom flask, equipped with an overhead mechanical stirrer, a nitrogen inlet, a condenser, placed inside a heating mantle, was charged with 1-ethynyl-4-fluorobenzene (500 g, 4.165 Mol), 1-fluoro-4-iodobenzene (715 g, 3.23 Mol), 22.5 g of dichlorobis(triphenylphosphine)palladium[II] catalyst, 6 g of copper[I] iodide, 8 g of triphenylphosphine, and 800 mL of anhydrous triethylamine. This was heated to reflux (~88° C. ) with stirring. Heating continued for 1 hour after which a gas chromatograph sample showed <1% starting material remained. The reaction mixture was cooled and the copious precipitate was filtered. The solids were washed with dry triethylamine. The combined triethylamine solutions were concentrated on the rotary evaporator and the brown residue was taken up in a minimum of dichloromethane. This was placed on a silica gel plug (about 1.5 kg) and eluted with hexanes (8L). The hexane fractions were concentrated on the rotary evaporator. The solid was recrystallized from methanol. The recrystallized solid, now a pale yellow material, was taken up in portions with hexane and the solution run through another silica gel plug (about 2 kg). The first 8L were clear, the next 16L (using recycled hexane) were yellow. The clear solutions were combined and stripped of solvent to yield a white solid. The yellow solutions were run through another clean silica gel plug to give a clear solution. This was stripped of solvent to give a white solid. The white solids were combined and dried to constant weight in a vacuum oven giving 648 g of the final product. (73% yield, m.p. 95°-97° C.).

Workup

  1. customA 2-Liter 4-neck round-bottom flask, equipped with an overhead mechanical stirrer, a nitrogen inlet, a condenser
  2. temperatureThis was heated
  3. temperatureto reflux (~88° C. )
  4. temperatureHeating
  5. temperatureThe reaction mixture was cooled
  6. filtrationthe copious precipitate was filtered
  7. washThe solids were washed with dry triethylamine
  8. concentrationThe combined triethylamine solutions were concentrated on the rotary evaporator
  9. washeluted with hexanes (8L)
  10. concentrationThe hexane fractions were concentrated on the rotary evaporator
  11. customThe solid was recrystallized from methanol
  12. customto yield a white solid
  13. customto give a clear solution
  14. customto give a white solid
  15. customdried to constant weight in a vacuum oven

Sources & evidence

ORD record
ord-7494446fe0b14dd0ad41ac0c29980c80
Source dataset
uspto-grants-2000_09
Patent number
US06124421

Reaction notes

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