3,5-Dibromopicolinonitrile → HCID 59799017, compound

HRID 2364548Notes

Reaction equation

HRID 2364548 reaction equation
[Br:1][C:2]1[C:3]([C:9]#[N:10])=[N:4][CH:5]=[C:6](Br)[CH:7]=1.[Cl-].[F:12][C:13]1[CH:20]=[CH:19][C:16]([CH2:17][Zn+])=[CH:15][CH:14]=1>O1CCCC1.O.C(OCC)(=O)C.Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd]>[Br:1][C:2]1[C:3]([C:9]#[N:10])=[N:4][CH:5]=[C:6]([CH2:17][C:16]2[CH:19]=[CH:20][C:13]([F:12])=[CH:14][CH:15]=2)[CH:7]=1

Participants

8

Reactant 2

HCID 123612023,5-DibromopicolinonitrileHCID 178505764HCID 178505764, compound2×

Product 1

HCID 59799017HCID 59799017, compoundYield 57%

Reagents, catalysts & solvents 5

HCID 313Hydrochloric AcidCatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
85 °C

Procedure

3,5-dibromo-2-pyridinecarbonitrile (4.52g, 15.34 mmol) was dissolved in tetrahydrofuran (75 mL) and palladium tetrakis(triphenylphosphine) (0.887g, 0.767 mmol) and 4-fluorobenyl zinc chloride (46.02 mL, 0.5 M in tetrahydrofuran) were added. The mixture was heated at 85° C. for 1 hour. An additional 12.3 mL of 4-fluorobenyl zinc chloride was added and the reaction was heated 40 minutes and allowed to cool to ambient temperature. The mixture was diluted with water and ethyl acetate and several drops of 1 N hydrochloric acid were added and the reaction was extracted with ethyl acetate. The organics were washed with brine, dried over sodium sulfate and concentrated under reduced pressure. Purification by silica gel chromatography (0-100% ethyl acetate/hexanes gradient elution) gave 3-bromo-5-[(4-fluorophenyl)methyl]-2-pyridinecarbonitrile (2.54g, 57% yield) as a pale yellow solid. 1H NMR (CDCl3) δ 8.48 (s, 1 H), 7.74 (s, 1 H), 7.15-7.11 (m, 2 H), 7.07-7.02 (m, 2 H), 4.02 (s, 2 H); MS m/z 292 (M+1).

Workup

  1. temperaturethe reaction was heated 40 minutes
  2. temperatureto cool to ambient temperature
  3. additionwere added
  4. extractionthe reaction was extracted with ethyl acetate
  5. washThe organics were washed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customPurification
  9. washby silica gel chromatography (0-100% ethyl acetate/hexanes gradient elution)

Sources & evidence

ORD record
ord-5e30e92fbca941b8b54d2061640ccce4
Source dataset
uspto-grants-2014_04
Patent number
US08691991B2

Reaction notes

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