Diethylamine → 5-(3-Hydroxy-4-fluorophenylethynyl)-nicotinonitrile

HRID 606864Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 606864
[C:1]([C:3]1[CH:4]=[N:5][CH:6]=[C:7]([CH:10]=1)[C:8]#[N:9])#[CH:2].[F:11][C:12]1[CH:17]=[CH:16][C:15](I)=[CH:14][C:13]=1[OH:19].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.C(NCC)C>O1CCOCC1.C(OCC)C.[Cu]I>[OH:19][C:13]1[CH:14]=[C:15]([C:2]#[C:1][C:3]2[CH:4]=[N:5][CH:6]=[C:7]([CH:10]=2)[C:8]#[N:9])[CH:16]=[CH:17][C:12]=1[F:11]

Komponenten

8

Edukt 4

HCID 8021DiethylamineHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 224165635-EthynylnicotinonitrileHCID 469118322-Fluoro-5-iodophenol

Produkt 1

HCID 670478145-(3-Hydroxy-4-fluorophenylethynyl)-nicotinonitrileAusbeute 42 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 3283Diethyl EtherLösungsmittelHCID 312751,4-DioxaneLösungsmittel2×

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

Add bis(phenylnitrile)palladium (II) chloride (115 mg, 0.3 mmol) to a suspension of copper (I) iodide (38 mg, 0.2 mmol) in anhydrous 1,4-dioxane (1 mL) under nitrogen and stir for 10 min. Sequentially add 5-ethynyl-nicotinonitrile (1.28 g, 10 mmol), (prepared essentially as described in PREPARATION 4), 2-fluoro-5-iodophenol, (prepared essentially as described in PREPARATION 15), (2.37 g, 10 mmol) and tri-tert-butylphosphine (121 mg, 0.6 mmol) in 1,4-dioxane (5 mL) and diethylamine (2.1 mL, 12 mmol) to the reaction mixture and heat at 60° C. for 16 h. Cool to room temperature, dilute with diethyl ether, stir for 10 min and filter through diatomaceous earth. Wash the filtrate sequentially with water and an aqueous saturated solution of sodium chloride. Dry (magnesium sulfate), concentrate and purify by silica gel chromatography, eluting with 0:100 to 35:100 ethyl acetate:hexanes, to give the title compound (1.0 g, 42%) as a yellow solid.

Aufarbeitung

  1. custom(prepared essentially
  2. temperatureCool to room temperature
  3. stirringstir for 10 min
  4. filtrationfilter through diatomaceous earth
  5. washWash the filtrate sequentially with water
  6. dry with materialDry (magnesium sulfate)
  7. concentrationconcentrate
  8. custompurify by silica gel chromatography
  9. washeluting with 0:100 to 35:100 ethyl acetate

Quellen und Nachweise

ORD-Eintrag
ord-c26e31154fe543f8a304049fba5b5ba6
Quelldatensatz
uspto-grants-2011_03
Patentnummer
US07915424B2

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