Ammonia → 1-(3,4,5-trimethoxybenzoyl)-3-(2-(4-(1H-benzimidazol-2-yl-amino)piperidin-1-yl)ethyl)-3-phenylpyrrolidine

Participants

Reaction Steps

Combine 1-(3,4,5-trimethoxybenzoyl)-3-phenyl-3-(2-methanesulfonyloxyethyl)pyrrolidine (prepared from (−)-3-phenyl-3-(2-hydroxyethyl)pyrrolidine (R,R)-di-p-anisoyltartaric acid salt) (2.51 g, 5.4 mmol), (1H-benzimidazol-2-yl)(piperidin-4-yl)amine hydriodic acid salt (3.07 g, 6.5 mmol), N,N-diisopropylethylamine (4.8 mL, 27.6 mmol), and acetonitrile (70 mL). Heat to reflux. After 18 hours, cool to ambient temperature, dilute the reaction mixture with ethyl acetate, and extract with water and brine. Separate the organic layer, dry over Na2SO4, filter, and evaporate in vacuo to give a residue. Chromatograph the residue on silica gel eluting with 305 methanol/ethyl acetate containing concentrated aqueous ammonia 22 mL/3L. Evaporate the product containing fractions to give a residue. Combine the residue and dichloromethane, filter and evaporate in vacuo to give the title compound: Rf=0.17 (silica gel, 30% methanol/ethyl acetate).

Provenance & Evidence