Cesium fluoride → 1-(2-{4-[2-(3,5-Dimethyl-4-methylsulfonyl-phenyl)-6-methoxy-naphthalen-1-yloxy]-phenoxy}-ethyl)-piperidine

HRID 748967Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 748967
C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.[F-].[Cs+].[CH2:22]([O:29][C:30]1[CH:31]=[CH:32][C:33]2[C:37]([O:38][C:39]3[CH:53]=[CH:52][C:42]([O:43][CH2:44][CH2:45][N:46]4[CH2:51][CH2:50][CH2:49][CH2:48][CH2:47]4)=[CH:41][CH:40]=3)=[C:36]([C:54]3[CH:59]=CC(S(C)(=O)=O)=C(F)C=3)S[C:34]=2[CH:65]=1)C1C=CC=CC=1.B1(B2OCC(C)(C)CO2)OCC(C)(C)CO1.Br[C:83]1[CH:84]=[C:85]([CH3:94])[C:86]([S:90]([CH3:93])(=[O:92])=[O:91])=[C:87]([CH3:89])[CH:88]=1>C(#N)C.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:94][C:85]1[CH:84]=[C:83]([C:36]2[CH:54]=[CH:59][C:34]3[C:33](=[CH:32][CH:31]=[C:30]([O:29][CH3:22])[CH:65]=3)[C:37]=2[O:38][C:39]2[CH:40]=[CH:41][C:42]([O:43][CH2:44][CH2:45][N:46]3[CH2:51][CH2:50][CH2:49][CH2:48][CH2:47]3)=[CH:52][CH:53]=2)[CH:88]=[C:87]([CH3:89])[C:86]=1[S:90]([CH3:93])(=[O:92])=[O:91]

Komponenten

9

Edukt 5

HCID 25953Cesium fluorideHCID 75806TricyclohexylphosphineHCID 2734316Bis(neopentyl glycolato)diboronHCID 59751449(2-{4-[6-Benzyloxy-2-(3-fluoro-4-methanesulfonyl-phenyl)-benzo[b]thiophen-3-yloxy]-phenoxy}-ethyl)-piperidineHCID 685159425-Bromo-2-methanesulfonyl-1,3-dimethyl-benzene

Produkt 1

HCID 597514541-(2-{4-[2-(3,5-Dimethyl-4-methylsulfonyl-phenyl)-6-methoxy-naphthalen-1-yloxy]-phenoxy}-ethyl)-piperidineAusbeute 84,6 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 6342AcetonitrileLösungsmittel2×HCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

Combine palladium (II) acetate (13 mg, 0.06 mmol), tricyclohexylphosphine (27 mg, 0.10 mmol), cesium fluoride (518 mg, 3.4 mmol) and acetonitrile (10 mL). Stir for 5 minutes. Add the compound of Preparation 1 (200 mg, 0.38 mmol) and bis(neopentylglycolato)diboron (129 mg, 0.57 mmol). Heat to 90° C. for 1 minute and add 5-bromo-2-methanesulfonyl-1,3-dimethyl-benzene (110 mg, 0.42 mmol) in acetonitrile (4 mL). Stir at 90° C. for 10 minutes. Cool to room temperature and dilute the solution with ethyl acetate (20 mL) and wash with saturated aqueous NaHCO3 (10 mL). Separate the layers, wash the organic layer with brine, dry with MgSO4, filter, and concentrate in vacuo. Chromatograph the residue on a SiO2 column eluting with methanol (4%) in dichloromethane to give 180 mg (76%) of the title compound. Mass spectrum (ion spray): m/z=560.3 (M+H).

Aufarbeitung

  1. additionAdd
  2. stirringStir at 90° C. for 10 minutes
  3. temperatureCool to room temperature
  4. washwash with saturated aqueous NaHCO3 (10 mL)
  5. customSeparate the layers
  6. washwash the organic layer with brine
  7. dry with materialdry with MgSO4
  8. filtrationfilter
  9. concentrationconcentrate in vacuo
  10. washChromatograph the residue on a SiO2 column eluting with methanol (4%) in dichloromethane

Quellen und Nachweise

ORD-Eintrag
ord-cff54c2a8af9425e8388dc31b2d76daf
Quelldatensatz
uspto-grants-2008_07
Patentnummer
US07399867B2

Notizen zur Reaktion

Wird geladen…