Cesium fluoride → 1-[2-[4-[[6-Methoxy-2-(5-methylsulfonyl-3-thienyl)-1-naphthyl]oxy]phenoxy]ethyl]piperidine

HRID 445223Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 445223
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]([O:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][N:23]3[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]3)=[CH:16][CH:15]=1)=[C:8](OS(C(F)(F)F)(=O)=O)[CH:7]=[CH:6]2.C[Sn](C)(C)[C:39]1[CH:43]=[C:42]([S:44]([CH3:47])(=[O:46])=[O:45])[S:41][CH:40]=1.[F-].[Cs+]>C(#N)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.[Pd]>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]([O:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][N:23]3[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]3)=[CH:16][CH:15]=1)=[C:8]([C:39]1[CH:43]=[C:42]([S:44]([CH3:47])(=[O:46])=[O:45])[S:41][CH:40]=1)[CH:7]=[CH:6]2

Komponenten

7

Edukt 3

HCID 25953Cesium fluorideHCID 116133766-Methoxy-1-(4-(2-(piperidin-1-yl)ethoxy)phenoxy)naphthalen-2-yl trifluoromethanesulfonateHCID 58338539Trimethyl-(5-methylsulfonyl-3-thienyl)stannane

Produkt 1

HCID 583385611-[2-[4-[[6-Methoxy-2-(5-methylsulfonyl-3-thienyl)-1-naphthyl]oxy]phenoxy]ethyl]piperidineAusbeute 57,9 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 23938PalladiumKatalysatorHCID 167845palladium(II) acetateKatalysatorHCID 6342AcetonitrileLösungsmittel2×

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

Combine palladium(II)acetate (0.043 g 0.19 mmol) and trycyclohexylphosphine (0.081 g, 0.29 mmol) in acetonitrile (15 mL) and sonicate for 10 minutes. Add [6-methoxy-1-[4-[2-(1-piperidyl)ethoxy]phenoxy]-2-naphthyl]trifluoromethanesulfonate (0.5 g, 0.95 mmol), trimethyl-(5-methylsulfonyl-3-thienyl)stannane (0.94 g, 2.9 mmol) and palladium mixture to a suspension of cesium fluoride (0.5 g, 3.3 mmol) in acetonitrile (40 mL). Warm the resulting mixture to 90° C. and stir for 18 hours. Cool the mixture to room temperature and concentrate. Partition the resulting residue between ethylacetate and saturated aqueous sodium bicarbonate. Separate the layers and wash the organic layer with saturated aqueous ammonium chloride and brine, then dry with sodium sulfate. Concentrate the resulting solution and purify by flash chromatography (0-5% methanol in dichloromethane) to obtain the title compound (0.3 g, 0.55 mmol).

Aufarbeitung

  1. customsonicate for 10 minutes
  2. temperatureCool the mixture to room temperature
  3. concentrationconcentrate
  4. customPartition the resulting residue between ethylacetate and saturated aqueous sodium bicarbonate
  5. customSeparate the layers
  6. washwash the organic layer with saturated aqueous ammonium chloride and brine
  7. dry with materialdry with sodium sulfate
  8. concentrationConcentrate the resulting solution
  9. custompurify by flash chromatography (0-5% methanol in dichloromethane)

Quellen und Nachweise

ORD-Eintrag
ord-0deb72a22e974dd38dda7abf22a2a45f
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08476300B2

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