Ethyl Acetate → 2-Thien-2-ylisonicotinonitrile

HRID 499325Notes

Reaction equation

HRID 499325 reaction equation
Cl[C:2]1[CH:7]=[C:6]([C:8]#[N:9])[CH:5]=[CH:4][N:3]=1.[S:10]1[CH:14]=[CH:13][CH:12]=[C:11]1OB(O)O.C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>C1(C)C(CCO)=CC=CC=1.O.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>[S:10]1[CH:14]=[CH:13][CH:12]=[C:11]1[C:2]1[CH:7]=[C:6]([CH:5]=[CH:4][N:3]=1)[C:8]#[N:9]

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 5686382-Chloro-4-cyanopyridineHCID 151389982-Thienylboric acid

Product 1

HCID 510640162-Thien-2-ylisonicotinonitrileYield 52.2%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 882672-Methylphenethyl alcoholSolvent

Procedure

2-Chloro-4-cyanopyridine (0.50 g, 3.6 mmol) and 2-thienylboric acid (0.69 g, 5.4 mmol) were dissolved in toluene-ethanol (4:1, v/v, 25 ml), and to the mixture, a solution of potassium carbonate (1.3 g, 9.0 mmol) in water (5 ml) was added. The mixture was deairated under reduced pressure for 15 minutes. Tetrakis(triphenylphosphine)palladium (0.21 mg, 0.2 mmol) was added to the mixture under nitrogen atmosphere, and the mixture was refluxed for 20 hrs. The reaction mixture was combined with ethyl acetate and water. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was subjected to a silica gel (60 g) column chromatography and eluted with hexane-ethyl acetate (3:1, v/v) to give solid, which was recrystallized from ethanol to give the titled compound (0.35 g, 52%).

Workup

  1. temperaturethe mixture was refluxed for 20 hrs
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. washeluted with hexane-ethyl acetate (3:1
  6. customv/v) to give solid, which
  7. customwas recrystallized from ethanol

Sources & evidence

ORD record
ord-0218e8ad33104ecd8521bf4642f68f22
Source dataset
uspto-grants-2010_08
Patent number
US07767665B2

Reaction notes

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