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

HRID 2232977Notes

Reaction equation

HRID 2232977 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 evaporation to give a brown oil. The product was purified by recrystallization from ethyl acetate/hexanes to give 417 mg (56%) of the title compound. 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 evaporation
  10. customto give a brown oil
  11. customThe product was purified by recrystallization from ethyl acetate/hexanes

Sources & evidence

ORD record
ord-361b3bff331c4e6eb42f111661b4a1f8
Source dataset
uspto-grants-2010_05
Patent number
US07709469B2

Reaction notes

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