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

Participants

Reaction Conditions

Reaction Steps

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).

Provenance & Evidence