2,4-Dichloropyrimidine → 2-Chloro-4-[2-(4-fluorophenyl)ethynyl]pyrimidine
Reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[CH:4][N:3]=1.[C:9]([C:11]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=1)#[CH:10]>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>[Cl:1][C:2]1[N:7]=[C:6]([C:10]#[C:9][C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)[CH:5]=[CH:4][N:3]=1Participants
6
Procedure
2,4-Dichloropyrimidine (50.0 g, 333 mmol) and 1-ethynyl-4-fluorobenzene (40.0 g, 333 mmol) were added to triethylamine (200 mL) at 25° C. To the reaction mixture were added dichlorobis(triphenylphosphine)palladium(II) (1.0 g, 1.4 mmol) and copper iodide (1.0 g, 5.2 mmol). The reaction mixture was stirred under a nitrogen atmosphere at room temperature for 18 h. The residue was partitioned between water (400 mL) and dichloromethane (400 mL). The organic layer was washed with water (2×400 mL), dried (MgSO4) and evaporated under reduced pressure to give an oil. Flash chromatographic purification on silica gel with 0 to 50% ethyl acetate/hexanes as eluant gave 69.5 g of the title compound as a light brown solid.
Workup
- customThe residue was partitioned between water (400 mL) and dichloromethane (400 mL)
- washThe organic layer was washed with water (2×400 mL)
- dry with materialdried (MgSO4)
- customevaporated under reduced pressure
- customto give an oil
- customFlash chromatographic purification on silica gel with 0 to 50% ethyl acetate/hexanes as eluant
Sources & evidence
- ORD record
- ord-f28a9b5895bd439991f00c564782c4df
- Source dataset
- uspto-grants-2012_10
- Patent number
- US08288375B2
Reaction notes
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