Reaktion #410362

Reaktionsgleichung

(1H-benzimidazol-2-yl)(1-benzylpiperidin-4-yl)amine

2-chloroethyl ethyl ether

potassium bis(trimethylsilyl)amide

2-chloroethyl ethyl ether

tetrahydrofuran

→

(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl)(1-benzylpiperidin-4-yl)amine

Lösungsmittel

water

triethylamine

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONAdd dropwise
2. 2
   TemperaturWarm to ambient temperature
3. 3
   Temperaturheat to reflux
4. 4
   workup.WAITAfter 4 hours
5. 5
   workup.WAITAfter 12 hours
6. 6
   Temperaturcool to ambient temperature
7. 7
   SonstigeSeparate the organic layer
8. 8
   Extraktionextract the aqueous layer with dichloromethane
9. 9
   TrocknenDry the combined organic layers over Na2SO4
10. 10
    Filtrationfilter
11. 11
    Sonstigeevaporate in vacuo
12. 12
    Sonstigeto give a residue

Vorschrift

Combine (1H-benzimidazol-2-yl)(1-benzylpiperidin-4-yl)amine (0.5 g, 1.6 mmol) and tetrahydrofuran (10 mL). Cool to −78° C. Add dropwise, a solution of potassium bis(trimethylsilyl)amide (3.6 mL, 0.5 M in toluene, 1.8 mmol). After 30 minutes, add 2-chloroethyl ethyl ether (0.2 g, 1.8 mmol). Warm to ambient temperature and heat to reflux. After 4 hours, add 2-chloroethyl ethyl ether (0.2 g, 1.8 mmol) and tetrabutylammonium bromide (0.1 g). After 12 hours, cool to ambient temperature and add water. Separate the organic layer and extract the aqueous layer with dichloromethane. 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/10% methanol/ethyl acetate to give (1-(2-ethoxyethyl)-1H-benzimidazol-2-yl)(1-benzylpiperidin-4-yl)amine: Rf=0.55 (2% triethylamine/10% methanol/ethyl acetate).

Quelle