Acetonitrile → A-431404

HRID 494820

Reaktionsgleichung

Reaktionsgleichung von HRID 494820
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:10]2[CH:15]=[CH:14][C:13]([OH:16])=[C:12](I)[CH:11]=2)=[O:9])=[CH:4][CH:3]=1.[CH2:18]([N:22]1[CH2:26][CH2:25][CH2:24][C@H:23]1[CH3:27])[CH2:19][C:20]#[CH:21].C(#N)C.CC1C=CC(P(C2C=CC(C)=CC=2)C2C=CC(C)=CC=2)=CC=1.C(NC(C)C)(C)C>CC([O-])=O.CC([O-])=O.[Pd+2].[Cu](I)I>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:10]2[CH:15]=[CH:14][C:13]3[O:16][C:20]([CH2:19][CH2:18][N:22]4[CH2:26][CH2:25][CH2:24][C@H:23]4[CH3:27])=[CH:21][C:12]=3[CH:11]=2)=[O:9])=[CH:4][CH:3]=1

Komponenten

8

Edukt 5

HCID 6342AcetonitrileHCID 7912DiisopropylamineHCID 13956Phosphine, tris(4-methylphenyl)-HCID 11367023(R)-1-(But-3-yn-1-yl)-2-methylpyrrolidineHCID 11382275(4-Fluorophenyl)(4-hydroxy-3-iodophenyl)methanone

Produkt 1

HCID 9906447A-431404Ausbeute 18 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 83717Copper iodideKatalysatorHCID 167845palladium(II) acetateKatalysator

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

The product from Example 68A (6.5 g, 18.5 mmol) was sequentially treated with a 0.1 M solution of the product from Example 68B in acetonitrile (230 mL, 23.0 mmol), Pd(OAc)2 (0.127 g, 0.566 mmol), tris(4-methylphenyl)phosphine (0.344 g, 1.130 mmol), and copper iodide (1.08 g, 95.72 mmol). After stirring at 25° C. for 10 minutes, the reaction mixture was treated with diisopropyl amine (26.6 mL, 189 mmol) and then heated at 60° C. in an inert atmosphere for 16 hours. The reaction mixture was allowed to cool to room temperature, filtered through celite, and the filtrate concentrated under reduced pressure. The residue was purified on silica gel using 90% DCM, 9.9% MeOH, 0.1% NH4OH to provide the title compound (1.21 g, 18.0% yield). 1HNMR (300 MHz, CD3OD) δ 1.09 (d, 3H, J=6.1 Hz), 1.46 (m, 1H), 1.81 (m, 2H), 2.02-2.28 (m, 2H), 2.49 (m, 2H) 3.06 (m, 2H), 3.28 (m, 2H), 6.68 (s, 1H), 7.27 (t, 2H), 7.58 (d, 1H, J=8.9 Hz), 7.71 (d, 1H, J=8.9 Hz) 7.86 (t, 2H), 7.97 (s, 1H); MS (ESI) m/z 352 (M+H)+.

Aufarbeitung

  1. temperatureheated at 60° C. in an inert atmosphere for 16 hours
  2. temperatureto cool to room temperature
  3. filtrationfiltered through celite
  4. concentrationthe filtrate concentrated under reduced pressure
  5. customThe residue was purified on silica gel using 90% DCM, 9.9% MeOH, 0.1% NH4OH

Quellen und Nachweise

ORD-Eintrag
ord-c361cf1ba6364ffeb5414b4f31dfc24f
Quelldatensatz
uspto-grants-2009_05
Patentnummer
US07538138B2

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