2-Chloronicotinonitrile → 2-(Thiophen-3-yl)pyridine-3-carbonitrile

HRID 1035067Notes

Reaction equation

HRID 1035067 reaction equation
[F-].[K+].Cl[C:4]1[C:9]([C:10]#[N:11])=[CH:8][CH:7]=[CH:6][N:5]=1.[S:12]1[CH:16]=[CH:15][C:14](B(O)O)=[CH:13]1>CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[S:12]1[CH:16]=[CH:15][C:14]([C:4]2[N:5]=[CH:6][CH:7]=[CH:8][C:9]=2[C:10]#[N:11])=[CH:13]1

Participants

6

Reactant 3

HCID 810792-ChloronicotinonitrileHCID 522689Potassium FluorideHCID 581760Thiophene-3-boronic acid

Product 1

HCID 185261682-(Thiophen-3-yl)pyridine-3-carbonitrileYield 56%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 178418851HCID 178418851, compoundCatalyst

Conditions

Temperature
90 °C

Procedure

To an oven-dried, N2-purged, 50 mL, round-bottomed flask containing a magnetic stir bar were added potassium fluoride (767 mg, 13.2 mmol), bis(tri-t-butylphosphine)palladium (51.0 mg, 0.10 mmol), tris(dibenzylideneacetone)dipalladium 46 mg, 0.05 mmol), 2-chloro-3-cyanopyridine (559 mg, 4.00 mmol), and 3-thiopheneboronic acid (819 mg, 6.4 mmol). The flask was sealed with a septum and purged with dry N2 atmosphere. Anhydrous dioxane (4 mL) was added via syringe. The reaction mixture was heated to ˜90° C. in an oil bath for 18 hours. After cooling to room temperature, ethyl acetate (15 mL) was added and the mixture was filtered through a pad of silica. The filtrate was concentrated by rotary evaporator to give a brown oil. The product was purified by recrystallization from ethyl acetate/hexanes to give 417 mg (56%) of the title compound as a beige solid. MS (ESI−) m/z 186.9 (M+H)+; 1H NMR (CDCl3) δ 7.30 (7.8, 4.7 Hz, 1H), 7.44 (dd, J=5.3, 2.9 Hz, 1H), 7.88 (dd, J=5.1, 1.4 Hz, 1H), 8.03 (dd, J=8.0, 1.9 Hz, 1H), 8.29 (dd, J=3.0, 1.4 Hz, 1H), 8.82 (dd, J=4.7, 1.7 Hz, 1H).

Workup

  1. customTo an oven-dried, N2-purged
  2. addition50 mL, round-bottomed flask containing a magnetic stir bar
  3. customThe flask was sealed with a septum
  4. custompurged with dry N2 atmosphere
  5. additionAnhydrous dioxane (4 mL) was added via syringe
  6. temperatureAfter cooling to room temperature
  7. additionethyl acetate (15 mL) was added
  8. filtrationthe mixture was filtered through a pad of silica
  9. concentrationThe filtrate was concentrated by rotary evaporator
  10. customto give a brown oil
  11. customThe product was purified by recrystallization from ethyl acetate/hexanes

Sources & evidence

ORD record
ord-1ec08313707b40139aadc0d7f75fbfa5
Source dataset
uspto-grants-2013_10
Patent number
US08546374B2

Reaction notes

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