Tetrahydrofuran → Ammonium Hydroxide

Participants

Reaction Steps

A solution of 4-[[1-[2-(1-methylethoxy)phenyl]-4-piperazinyl]methyl]benzyl chloride hydrochloride (5.0 g, 0.012 mol), pyrrolidine (8.95 g, 0.126 mol), excess triethylamine, and THF (50 mL) was stirred at room temperature for 24 h. The reaction was then diluted with methylene chloride and washed with water. The organic layer was separated, dried (Na2SO4), filtered, and evaporated to a yellow oil. The residue was chromatographed on silica gel using 95:4.5:0.5/CHCl3:MeOH:NH4OH as eluant to give 1-[[4-[[1-[2-(1-methylethoxy)phenyl]-4-piperazinyl]methyl]phenyl]methyl]pyrrolidine as an oil, 5.00 g (100%). This material (4.95 g, 0.013 mol) was dissolved in i-PrOH (100 mL) and acidified with concentrated HCl to pH 3. The resulting solid was collected by filtration to give 1-[[4-[[1-[2-(1-methylethoxy)phenyl]-4-piperazinyl]methyl]phenyl]methyl]pyrrolidine dihydrochloride hydrate as a white powder, 4.83 g (80%), m.p. 270-280 (browning) 280°-300° C. 1H NMR and mass spectral analysis supported the assigned structure.

Provenance & Evidence