Potassium tert-butoxide → SUN 1334H

Participants

Reaction Steps

To a stirred solution of 4-{4-[bis-(4-fluorophenyl)methyl]piperazin-1-yl}-(E)-but-2-en-1-ol (247.0 g, 0.689 mol) and potassium tert-butoxide (139.2 g, 1.240 mol) in anhydrous tert-butanol (2000 ml), preheated at 60-65° C. for 1 hr. under nitrogen atmosphere, is added dry sodium chloroacetate (160.5 g, 1.378 mol). The reaction mass is then refluxed for further 5 hrs. The mixture is then concentrated under reduced pressure at below 60° C. until tert-butanol is completely removed. The residue is taken up in water (1500 ml) and washed with ethyl acetate (2×1500 ml). The aqueous solution is then acidified to pH 5-6, extracted into dichloromethane (2×750 ml), washed dichloromethane layer with water (300 ml), and concentrated to get crude product as a foamy solid. The crude product is purified by flash column chromatography on silica gel using toluene-methanol (4:1) as mobile phase. The product was converted to its dihydrochloride salt as in example 17.

Provenance & Evidence