Potassium Carbonate → 6-[(5-Chloro-2-{[(4-chloro-2-fluorophenyl)methyl]oxy}phenyl)methyl]-3-methyl-2-pyridinecarbonitrile

HRID 2356635

Reaction equation

HRID 2356635 reaction equation
Cl[CH2:2][C:3]1[N:8]=[C:7]([C:9]#[N:10])[C:6]([CH3:11])=[CH:5][CH:4]=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](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])[C:6]([CH3:11])=[CH:5][CH:4]=2)[CH:18]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 55298148HCID 55298148, compoundHCID 59384250(5-Chloro-2-{[(4-chloro-2-fluorophenyl)methyl]oxy}phenyl)boronic acid

Product 1

HCID 684565876-[(5-Chloro-2-{[(4-chloro-2-fluorophenyl)methyl]oxy}phenyl)methyl]-3-methyl-2-pyridinecarbonitrileYield 64%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Procedure

To a solution of 6-(Chloromethyl)-3-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 2.5 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 (204 mg, 64%) as a white solid.

Workup

  1. temperatureunder reflux for 2.5 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-5f54190645cd482d812a81eec6280f73
Source dataset
uspto-grants-2010_07
Patent number
US07759369B2

Linked notes

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