Reaktion #410455

ord-c8823596a44a4c9fbcc6f6d4df2647a2

Lösungsmittel

Reaktionsbedingungen

Temperatur
-78°CELSIUS
Detaillierte Bedingungen
See reaction.notes.procedure_details.

Aufarbeitung

  1. 1
    Temperaturwarm to ambient temperature
  2. 2
    TemperaturHeat to reflux
  3. 3
    workup.WAITAfter 12 hours
  4. 4
    Temperaturto reflux
  5. 5
    workup.WAITAfter 12 hours
  6. 6
    Temperaturcool
  7. 7
    Sonstigethe reaction
  8. 8
    SonstigeSeparate the layers
  9. 9
    Extraktionextract the aqueous layer three times with ethyl acetate
  10. 10
    TrocknenDry the combined organic layers over Na2SO4
  11. 11
    Filtrationfilter
  12. 12
    Sonstigeevaporate in vacuo
  13. 13
    Sonstigeto give a residue

Vorschrift

Combine 1-(3,4,5-trimethoxybenzoyl)-3-(2-(4-(1H-benzimidazol-2-yl-amino)piperidin-1-yl)ethyl)-3-(phenylmethyl)pyrrolidine (0.56 g, 0.77 mmol) and tetrahydrofuran (10 mL). Cool to −78° C. using a dry-ice/acetone bath. Add a solution of potassium bis(trimethylsilyl)amide (1.7 mL, 0.5 M in toluene, 0.85 mmol). After 30 minutes, warm to ambient temperature. Add tetrabutylammonium bromide (0.06 g) and 2-chloroethyl ethyl ether (0.092 g 0.85 mmol). Heat to reflux. After 12 hours, potassium bis(trimethylsilyl)amide (0.5 mL, 0.5 M in toluene) and 2-chloroethyl ethyl ether (0.5 mL) and continue to reflux. After 12 hours, cool the reaction and add water. Separate the layers and extract the aqueous layer three times with ethyl acetate. Dry the combined organic layers over Na2SO4, filter, and evaporate in vacuo to give a residue. Chromatograph the residue on silica gel eluting with 2% triethylamine/5% methanol/ethyl acetate to give the title compound: Rf=0.32 (silica gel, 2% triethylamine/5% methanol/ethyl acetate).

Quelle

DOI: 10.6084/m9.figshare.5104873.v1Patent: US06211199B1uspto-grants-2001_04