Triphenylphosphine → 4-[1-(4-Fluoro-phenyl)-2-methyl-1H-imidazol-4-ylethynyl]-2-methyl-pyridine

HRID 860151Notes

Reaction equation

HRID 860151 reaction equation
I[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([CH3:8])[CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:28]([C:30]1[N:31]=[C:32]([CH3:42])[N:33]([C:35]2[CH:40]=[CH:39][C:38]([F:41])=[CH:37][CH:36]=2)[CH:34]=1)#[CH:29]>C1COCC1.N1CCCCC1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Cu]I>[F:41][C:38]1[CH:37]=[CH:36][C:35]([N:33]2[CH:34]=[C:30]([C:28]#[C:29][C:2]3[CH:7]=[CH:6][N:5]=[C:4]([CH3:8])[CH:3]=3)[N:31]=[C:32]2[CH3:42])=[CH:40][CH:39]=1

Participants

8

Reactant 3

HCID 11776TriphenylphosphineHCID 116655954-Ethynyl-1-(4-fluorophenyl)-2-methyl-1H-imidazoleHCID 126913224-Iodo-2-methylpyridine

Product 1

HCID 100856604-[1-(4-Fluoro-phenyl)-2-methyl-1H-imidazol-4-ylethynyl]-2-methyl-pyridine

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 8028TetrahydrofuranSolventHCID 8082PiperidineSolvent

Procedure

4-Iodo-2-methyl-pyridine (656 mg, 3.0 mmol) was dissolved in 10 mL dry THF and 10 mL piperidine. This mixture was evacuated and backfilled with argon several times to remove oxygen from the solution. Triphenylphosphine (20 mg, 0.07 mmol) and bis(triphenylphosphin)palladium(II)chloride (175 mg, 0.10 mmol) were added and the reaction mixture was stirred at RT for 1 h. Copper(I)iodide (14 mg, 0.07 mmol) and 4-ethynyl-1-(4-fluoro-phenyl)-2-methyl-1H-imidazole (IV-1) (500 mg, 2.5 mmol) were added. The reaction mixture was then refluxed for 3 h. The solvent was evaporated. The residue was taken up in 30 mL water and extracted three times with ethyl acetate (50 mL each). The combined organic extracts were dried with magnesium sulfate, filtered and evaporated. The crude product was purified by flash chromatography on silica gel (dichloromethane/methanol 100:0→90:10 gradient) and recrystallization from diethylether and the desired product was obtained as a light yellow solid (250 mg, 34%), mp=151° C., MS: m/e=292.1 (M+H+).

Workup

  1. customThis mixture was evacuated
  2. customto remove oxygen from the solution
  3. temperatureThe reaction mixture was then refluxed for 3 h
  4. customThe solvent was evaporated
  5. extractionextracted three times with ethyl acetate (50 mL each)
  6. dry with materialThe combined organic extracts were dried with magnesium sulfate
  7. filtrationfiltered
  8. customevaporated
  9. customThe crude product was purified by flash chromatography on silica gel (dichloromethane/methanol 100:0→90:10 gradient) and recrystallization from diethylether

Sources & evidence

ORD record
ord-913b7c615b2140918a27975585bb4bce
Source dataset
uspto-grants-2006_12
Patent number
US07153874B2

Reaction notes

Loading…