Potassium Carbonate → 2-(3'-Chloro-3-fluorobiphenyl-4-yl)acetonitrile

HRID 70886Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 70886
Br[C:2]1[CH:10]=[CH:9][C:5]([CH2:6][C:7]#[N:8])=[C:4]([F:11])[CH:3]=1.[Cl:12][C:13]1[CH:14]=[C:15](B(O)O)[CH:16]=[CH:17][CH:18]=1.C([O-])([O-])=O.[K+].[K+]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.O.CCOC(C)=O.CC([O-])=O.CC([O-])=O.[Pd+2]>[Cl:12][C:13]1[CH:18]=[C:17]([C:2]2[CH:10]=[CH:9][C:5]([CH2:6][C:7]#[N:8])=[C:4]([F:11])[CH:3]=2)[CH:16]=[CH:15][CH:14]=1

Komponenten

8

Edukt 3

HCID 11430Potassium CarbonateHCID 2734323(3-Chlorophenyl)boronic acidHCID 71723082-(4-Bromo-2-fluorophenyl)acetonitrile

Produkt 1

HCID 596077962-(3'-Chloro-3-fluorobiphenyl-4-yl)acetonitrileAusbeute 87,6 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 74236Tetrabutylammonium BromideKatalysatorHCID 167845palladium(II) acetateKatalysatorHCID 962WaterLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

A suspension of 4-bromo-2-fluorobenzyl cyanide (3.50 g, 16.35 mmol), 3-chlorobenzeneboronic acid (2.68 g, 17.17 mmol), Pd(OAc)2 (0.110 g, 0.491 mmol), K2CO3 (5.65 g, 40.9 mmol) and tetrabutylammonium bromide (5.80 g, 17.99 mmol) in water (14 ml) is allowed to stir under nitrogen at 70° C. for 1 hour. The reaction mixture is cooled to room temperature, and diluted with EtOAc. The two phases are separated. The organic layer is washed with brine, dried over MgSO4, filtered and concentrated. The obtained residue is purified by silica gel flash column chromatography (heptane/EtOAc=100:0 to 70:30) to give 2-(3′-chloro-3-fluorobiphenyl-4-yl)acetonitrile (3.52 g); HPLC retention time=1.17 minutes (condition B); 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 3.81 (s, 2 H) 7.29-7.45 (m, 5 H) 7.50-7.55 (m, 2 H).

Aufarbeitung

  1. temperatureThe reaction mixture is cooled to room temperature
  2. customThe two phases are separated
  3. washThe organic layer is washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe obtained residue is purified by silica gel flash column chromatography (heptane/EtOAc=100:0 to 70:30)

Quellen und Nachweise

ORD-Eintrag
ord-55e9ba74ea7a421b88130ab8228e81aa
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08822534B2

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