1-Ethynyl-4-fluorobenzene → 4-[2-(4-Fluorophenyl)ethynyl]-2-(methylthio)pyrimidine

HRID 2063250Notes

Reaction equation

HRID 2063250 reaction equation
I[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([S:8][CH3:9])[N:3]=1.[C:10]([C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=1)#[CH:11]>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.C(N(CC)CC)C>[F:18][C:15]1[CH:16]=[CH:17][C:12]([C:10]#[C:11][C:2]2[CH:7]=[CH:6][N:5]=[C:4]([S:8][CH3:9])[N:3]=2)=[CH:13][CH:14]=1

Participants

6

Reactant 2

HCID 5226271-Ethynyl-4-fluorobenzeneHCID 38589014-Iodo-2-(methylthio)pyrimidine

Product 1

HCID 226752434-[2-(4-Fluorophenyl)ethynyl]-2-(methylthio)pyrimidineYield 52.8%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8471TriethylamineSolvent

Procedure

4-Iodo-2-(methylthio)pyrimidine (35.7 g, 142 mmol) and 1-ethynyl-4-fluorobenzene (17.0 g, 142 mmol) were added to triethylamine (200 mL) at room temperature. To the resulting solution were added dichlorobis(triphenylphosphine)palladium(II) (1.0 g, 1.4 mmol) and copper iodide (1.0 g, 5.2 mmol). Then the reaction mixture was stirred under a nitrogen atmosphere at room temperature for 18 h. The reaction mixture was concentrated under reduced pressure to remove excess triethylamine. The residue was partitioned between water (400 mL) and dichloromethane (400 mL). The organic layer was washed with water (2×400 mL) and dried (MgSO4), and the solvent was evaporated under reduced pressure to give an oil. Flash chromatographic purification on silica gel with 0 to 50% ethyl acetate/hexanes as eluant gave 18.3 g of the title compound as a light brown solid.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customto remove excess triethylamine
  3. customThe residue was partitioned between water (400 mL) and dichloromethane (400 mL)
  4. washThe organic layer was washed with water (2×400 mL)
  5. dry with materialdried (MgSO4)
  6. customthe solvent was evaporated under reduced pressure
  7. customto give an oil
  8. customFlash chromatographic purification on silica gel with 0 to 50% ethyl acetate/hexanes as eluant

Sources & evidence

ORD record
ord-154121dcf388495b8141c48fbf696cbd
Source dataset
uspto-grants-2012_10
Patent number
US08288375B2

Reaction notes

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