1-(2-Bromo-5-fluoro-phenyl)-1H-pyrazole → 4-Fluoro-2-pyrazol-1-yl-benzonitrile

HRID 1726667Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1726667
[C:1]([Cu])#[N:2].Br[C:5]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][C:6]=1[N:12]1[CH:16]=[CH:15][CH:14]=[N:13]1>CN(C=O)C>[F:11][C:8]1[CH:9]=[CH:10][C:5]([C:1]#[N:2])=[C:6]([N:12]2[CH:16]=[CH:15][CH:14]=[N:13]2)[CH:7]=1

Komponenten

4

Edukt 2

HCID 210697661-(2-Bromo-5-fluoro-phenyl)-1H-pyrazoleHCID 178418546HCID 178418546, Verbindung

Produkt 1

HCID 210699164-Fluoro-2-pyrazol-1-yl-benzonitrileAusbeute 72,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel2×

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

To a stirred suspension of CuCN (358 mg, 4.0 mmol, Aldrich) in DMF (2 mL, Sure Seal) was added a solution of 1-(2-Bromo-5-fluoro-phenyl)-1H-pyrazole (964 mg, 4.0 mmol) in DMF (2 mL) and the resulting clear solution was stirred in an oil bath heated at 110° C. under nitrogen for 1.5 h. After cooling, the mixture was concentrated in vacuo and the residue mixed with 14% aqueous NH4OH (10 mL) was stirred at room temperature for 0.5 h. To this was added EtOAc (15 mL) and the mixture stirred for additional 0.5 h. The EtOAc extract was washed with dil. NH4OH and then with brine, dried (Na2SO4), filtered, and concentrated. The residual oil was purified by column chromatography (SiO2, 0-10% EtOAc/CH2Cl2) to obtain 542 mg of the title compound as a white crystalline solid: TLC Rf 0.42 (CH2Cl2); HPLC rt=1.94 min. LC/MS m/z 188 (M+H); 1H NMR (CDCl3, 500 MHz) δ ppm 6.55 (1H, dd, J=2.6, 1.7 Hz, 9-CH), 7.10-7.13 (1H, m, 5-CH), 7.59 (1H, dd, J=9.5, 2.5 Hz, 3-CH), 7.76 (1H, dd, J=8.7, 5.5 Hz, 6-CH), 7.80 (1H, d, J=−1.2 Hz, 10-CH), 8.25 (1H, d, J=2.7 Hz, 8-CH); 13C NMR (CDCl3, 125.8 Hz) δ ppm 100.5 (d, J=3.8 Hz, 1-C), 109.1 (9-CH), 111.9 (d, J=27 Hz, 3-CH), 114.9 (d, J=23 Hz, 5-CH), 116.6 (7-CN), 129.5 (8-CH), 136.7 (d, J=10 Hz, 6-CH), 142.8 (10-CH), 144.2 (d, J=12 Hz, 2-C), 165.5 (d, J=258 Hz, 4-CF); HRMS (ESI) calcd for C10H7FN3 (M+H) 189.0576, found 189.0568 (δ-4.5 ppm); UV (MeOH) λ max 224 nm (ε2.54×104), 261 nm (ε1.20×104); Anal. calcd for C10H7FN3: C, 64.16; H, 3.24; N, 22.45; found C, 64.02; H, 3.16; N, 22.68.

Aufarbeitung

  1. temperatureAfter cooling
  2. concentrationthe mixture was concentrated in vacuo
  3. additionthe residue mixed with 14% aqueous NH4OH (10 mL)
  4. stirringwas stirred at room temperature for 0.5 h
  5. additionTo this was added EtOAc (15 mL)
  6. stirringthe mixture stirred for additional 0.5 h
  7. extractionThe EtOAc extract
  8. washwas washed with dil. NH4OH
  9. dry with materialwith brine, dried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe residual oil was purified by column chromatography (SiO2, 0-10% EtOAc/CH2Cl2)

Quellen und Nachweise

ORD-Eintrag
ord-7bf3c1bf2fde4bf2b8f86c0cd43b87bf
Quelldatensatz
uspto-grants-2009_02
Patentnummer
US07491819B1

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