Potassium Carbonate → 6-[(5-Chloro-2-{[(4-chloro-2-fluorophenyl)methyl]oxy}phenyl)methyl]-5-methyl-2-pyridinecarbonitrile

HRID 2356629

Reaction equation

HRID 2356629 reaction equation
Cl[CH2:2][C:3]1[N:8]=[C:7]([C:9]#[N:10])[CH:6]=[CH:5][C:4]=1[CH3:11].[Cl:12][C:13]1[CH:14]=[CH:15][C:16]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][C:25]=2[F:31])=[C:17](B(O)O)[CH:18]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.C(O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:12][C:13]1[CH:14]=[CH:15][C:16]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][C:25]=2[F:31])=[C:17]([CH2:2][C:3]2[N:8]=[C:7]([C:9]#[N:10])[CH:6]=[CH:5][C:4]=2[CH3:11])[CH:18]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 55298147HCID 55298147, compoundHCID 59384250(5-Chloro-2-{[(4-chloro-2-fluorophenyl)methyl]oxy}phenyl)boronic acid

Product 1

HCID 684565816-[(5-Chloro-2-{[(4-chloro-2-fluorophenyl)methyl]oxy}phenyl)methyl]-5-methyl-2-pyridinecarbonitrileYield 40.5%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Procedure

To a solution of 6-(chloromethyl)-5-methyl-2-pyridinecarbonitrile (132.5 mg) in dry toluene (4 ml) and ethanol (4 ml) was added (5-chloro-2-{[(4-chloro-2-fluorophenyl)methyl]oxy}phenyl)boronic acid (250 mg), potassium carbonate (330 mg) and tetrakis(triphenylphosphine)palladium(0) (92 mg) and the mixture stirred under reflux for 2 hours. Solvent was removed in vacuo and water (20 ml) and ether (20 ml) added. Insoluble solid was filtered over Celite and washed with ether. The aqueous layer was further extracted with ether (15 ml) and the combined extracts washed with brine (10 ml), dried (MgSO4) and concentrated in vacuo. The residue was purified by mass-directed autopreparation to afford the title compound (129 mg, 40%) as a pale buff solid.

Workup

  1. temperatureunder reflux for 2 hours
  2. customSolvent was removed in vacuo and water (20 ml) and ether (20 ml)
  3. additionadded
  4. filtrationInsoluble solid was filtered over Celite
  5. washwashed with ether
  6. extractionThe aqueous layer was further extracted with ether (15 ml)
  7. washthe combined extracts washed with brine (10 ml)
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by mass-directed autopreparation

Sources & evidence

ORD record
ord-8659c4b73b3b4b6fa8cb304268e98b3b
Source dataset
uspto-grants-2010_07
Patent number
US07759369B2

Linked notes

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