Reaktion #410412

Reaktionsgleichung

1-(3,4,5-trimethoxybenzoyl)-3-(2-(4-(1H-benzimidazol-2-yl-amino)piperidin-1-yl)ethyl)-3-(3,4-dimethylphenyl)pyrrolidine

potassium bis(trimethylsilyl)amide

2-chloroethyl ethyl ether

tetrahydrofuran

→

title compound

1-(3,4,5-trimethoxybenzoyl)-3-(2-(4-(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl-amino)piperidin-1-yl)ethyl)-3-(3,4-dimethylphenyl)pyrrolidine

Lösungsmittel

dichloromethane

methanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturwarm to ambient temperature
2. 2
   TemperaturHeat to reflux
3. 3
   workup.WAITAfter 2 days
4. 4
   Temperaturcool the reaction mixture
5. 5
   ExtraktionExtract with water and saturated aqueous solution of sodium chloride
6. 6
   EinengenConcentrate the separated organic layer in vacuo
7. 7
   Sonstigeto give a residue

Vorschrift

Combine 1-(3,4,5-trimethoxybenzoyl)-3-(2-(4-(1H-benzimidazol-2-yl-amino)piperidin-1-yl)ethyl)-3-(3,4-dimethylphenyl)pyrrolidine (0.46 g, 0.76 mmol) and tetrahydrofuran (35 mL). Cool to −78° C. using a dry-ice/acetone bath. Add a solution of potassium bis(trimethylsilyl)amide (2.1 mL, 0.5 M in toluene, 1.05 mmol). After 20 minutes, warm to ambient temperature. Add tetrabutylammonium bromide (0.21 g, 0.65 mmol) and 2-chloroethyl ethyl ether (1 mL). Heat to reflux. After 2 days, cool the reaction mixture and dilute with dichloromethane. Extract with water and saturated aqueous solution of sodium chloride. Concentrate the separated organic layer in vacuo to give a residue. Chromatograph the residue on silica gel eluting with 28% methanol/0.7% concentrated aqueous ammonia/ethyl acetate to give the title compound: Rf=0.26 (silica gel, 30% methanol/ethyl acetate).

Quelle