1-(Difluoromethoxy)-4-iodobenzene → HCID 67538136, compound

HRID 2240938Notes

Reaction equation

HRID 2240938 reaction equation
[F:1][CH:2]([F:11])[O:3][C:4]1[CH:9]=[CH:8][C:7](I)=[CH:6][CH:5]=1.[C:12]([C:14]1[CH:15]=[CH:16][C:17]([F:25])=[C:18]([CH2:20][CH2:21][CH2:22][C:23]#[N:24])[CH:19]=1)#[CH:13]>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu](I)I>[F:1][CH:2]([F:11])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:13]#[C:12][C:14]2[CH:15]=[CH:16][C:17]([F:25])=[C:18]([CH2:20][CH2:21][CH2:22][C:23]#[N:24])[CH:19]=2)=[CH:6][CH:5]=1

Participants

6

Reactant 2

HCID 27370081-(Difluoromethoxy)-4-iodobenzeneHCID 59305338HCID 59305338, compound

Product 1

HCID 67538136HCID 67538136, compoundYield 90.3%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of 1-Difluoromethoxy-4-iodo-benzene (0.21 g, 0.79 mmol) in DMF (3.5 ml) were added TEA (0.55 mL, 57.4 mmol) and 4-(5-Ethynyl-2-fluoro-phenyl)-butyronitrile (0.48 g, 0.79 mmol). The reaction was degassed by bubbling argon through it for 5 min and then dichlorbis(triphenylphospine)palladium (0.0.28 g, 0.04 mmol), and copper iodide (0.008 g, 0.57 mmol) were added simultaneously. The reaction mixture was heated at 65° C. for 15 min. cooled and quenched with 0.1 N HCl (10 ml). The aqueous layer was extracted with Et2O (3×10 ml). The combined organic extracts were washed with brine (25 ml), dried (MgSO4), and concentrated. The crude material was purified by silica gel chromatography (10-20% Ethyl acetate/Petroleum Ether) to afford the titled compound (0.235 g, 90%) as a brown oil that solidified on standing, and was identified by NMR and mass spectral analyses. MS (EI+): 329 (M+).

Workup

  1. customThe reaction was degassed
  2. customby bubbling argon through it for 5 min
  3. temperaturecooled
  4. customquenched with 0.1 N HCl (10 ml)
  5. extractionThe aqueous layer was extracted with Et2O (3×10 ml)
  6. washThe combined organic extracts were washed with brine (25 ml)
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated
  9. customThe crude material was purified by silica gel chromatography (10-20% Ethyl acetate/Petroleum Ether)

Sources & evidence

ORD record
ord-74c9fb79ab7143b08b1786520567ba46
Source dataset
uspto-grants-2010_05
Patent number
US07723368B2

Reaction notes

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