Triphenylphosphine → HCID 11688761, compound

HRID 2067930Notes

Reaction equation

HRID 2067930 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6](I)[CH:5]=[CH:4][N:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[F:28][C:29]1[CH:34]=[C:33]([F:35])[CH:32]=[CH:31][C:30]=1[N:36]1[C:40]([CH3:41])=[C:39]([C:42]#[CH:43])[N:38]=[C:37]1[CH3:44]>C1COCC1.C(N(CC)CC)C.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>[Cl:1][C:2]1[CH:7]=[C:6]([C:43]#[C:42][C:39]2[N:38]=[C:37]([CH3:44])[N:36]([C:30]3[CH:31]=[CH:32][C:33]([F:35])=[CH:34][C:29]=3[F:28])[C:40]=2[CH3:41])[CH:5]=[CH:4][N:3]=1

Participants

8

Reactant 3

HCID 11776TriphenylphosphineHCID 15165112-Chloro-4-iodopyridineHCID 86602964HCID 86602964, compound

Product 1

HCID 11688761HCID 11688761, compound

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

2-Chloro-4-iodo-pyridine (0.21 g, 1 mmol) was dissolved in 10 mL of dry THF and 0.29 mL triethyl amine. This mixture was evacuated and backfilled with argon several times to remove oxygen from the solution. Triphenylphosphine (5 mg, 0.03 eq) and bis(triphenylphosphine)palladium(II)chloride (24 mg, 0.05 eq) were added, and the reaction mixture was stirred at room temperature for 10 min. 1-(2,4-Difluoro-phenyl)-4-ethynyl-2,5-dimethyl-1H-imidazole (0.16 g, 1 mmol) and Copper(I)iodide (3 mg, 0.02 eq) were added. The reaction mixture was stirred at room temperature overnight. The solvent was evaporated. The residue was taken up in 10 mL water and extracted three times with ethyl acetate (10 mL each). The combined organic extracts were dried with magnesium sulfate, filtered and evaporated. The crude product was purified by chromatography on silica gel (n-heptane/ethyl acetate 1:1) and recrystallized from diethyl ether. The desired product was obtained as a white solid (0.1 g, 42%), MS: m/e=344.0 (M+).

Workup

  1. customThis mixture was evacuated
  2. customto remove oxygen from the solution
  3. stirringThe reaction mixture was stirred at room temperature overnight
  4. customThe solvent was evaporated
  5. extractionextracted three times with ethyl acetate (10 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 chromatography on silica gel (n-heptane/ethyl acetate 1:1)
  10. customrecrystallized from diethyl ether

Sources & evidence

ORD record
ord-bcbeb0f6511d4ea5ae59ab15c6aafe19
Source dataset
uspto-grants-2012_10
Patent number
US08293916B2

Reaction notes

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