Ethyl Acetate → 3-[1-(2-Pyridinyl)-1H-pyrrol-3-yl]benzonitrile

HRID 2222265Notes

Reaction equation

HRID 2222265 reaction equation
Br[C:2]1[CH:6]=[CH:5][N:4]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=2)[CH:3]=1.[C:13]([C:15]1[CH:16]=[C:17](B(O)O)[CH:18]=[CH:19][CH:20]=1)#[N:14].C(=O)([O-])[O-].[K+].[K+].CCOC(C)=O>COCCOC.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>[N:8]1[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=1[N:4]1[CH:5]=[CH:6][C:2]([C:19]2[CH:20]=[C:15]([CH:16]=[CH:17][CH:18]=2)[C:13]#[N:14])=[CH:3]1

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 27343253-Cyanophenylboronic acid2×HCID 534231772-(3-Bromo-1H-pyrrol-1-yl)pyridine

Product 1

HCID 101310833-[1-(2-Pyridinyl)-1H-pyrrol-3-yl]benzonitrile

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
84 °C

Procedure

2-(3-Bromo-1H-pyrrol-1-yl)pyridine (1.34 g, 2 mmol), 3-cyanophenylboronic acid (0.59 g, 4 mmol), Pd(PPh3)4 (116 mg, 0.1 mmol) and potassium carbonate (560 mg, 4 mmol) were dissolved in a mixture of DME (18 mL) and H2O (2 mL) and degassed for 15 min with Ar (g). The reaction mixture was then heated at 84° C. for 18 h. At this time, a further 0.25 eq. of 3-cyanophenylboronic acid (0.15 g, 1 mmol) was added and heating was continued. After a total of 42 h, the reaction mixture was cooled to rt, H2O (40 mL) and EtOAc (40 mL) were added and the reaction mixture shaken, the EtOAc layer was separated and the aqueous layer shaken with EtOAc (2×30 mL). The combined organic layers were dried over Na2SO4 and concentrated to a yellow oil. This was purified by liquid chromatography on silica gel eluting with EtOAc:hexane (3:7) to afford a white waxy solid that was further purified by liquid chromatography on silica gel eluting with dichloromethane to afford 3-(1-pyridin-2-yl-1H-pyrrol-3-yl)benzonitrile as a colorless oil. 1H NMR (CD3Cl, 300 MHz) δ 8.49-8.52 (1H, m), 7.66 (1H, ddd), 7.47-7.51 (2H, m), 7.33-7.39 (3H, m), 7.24 (1H, ddd), 6.91 (1H, d), 6.51-6.52 (1H, m), 6.43 (1H, dd). MS (ESI) 246 (M+H)+.

Workup

  1. customdegassed for 15 min with Ar (g)
  2. temperatureheating
  3. temperatureAfter a total of 42 h, the reaction mixture was cooled to rt
  4. customthe EtOAc layer was separated
  5. stirringthe aqueous layer shaken with EtOAc (2×30 mL)
  6. dry with materialThe combined organic layers were dried over Na2SO4
  7. concentrationconcentrated to a yellow oil
  8. customThis was purified by liquid chromatography on silica gel eluting with EtOAc:hexane (3:7)
  9. customto afford a white waxy solid
  10. customthat was further purified by liquid chromatography on silica gel eluting with dichloromethane

Sources & evidence

ORD record
ord-69cc0e4ccf5649e68ff54e8cafc88081
Source dataset
uspto-grants-2008_05
Patent number
US07371767B2

Reaction notes

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