1-(2-[4-Chlorophenoxy]acetyl)-4-(3,4-methylenedioxybenzyl)piperazine

Originator

Attentil,Ravizza

Uses

Fipexide is one of five potential drug candidates to overcome the melphalan-induced vascular toxicity.

Uses

psychostimulant

Definition

ChEBI: 1-[4-(1,3-benzodioxol-5-ylmethyl)-1-piperazinyl]-2-(4-chlorophenoxy)ethanone is a member of benzodioxoles.

Manufacturing Process

25.8 g (0.3 moles) of anhydrous piperazine and 32.5 ml (1.8 moles) of distilled water (or simply 58.3 g (0.3 moles) of piperazine hexahydrate) are loaded into a 250 ml flask provided with an agitator, a thermometer and a reflux condenser, together with 51.2 g (0.3 moles) of piperonyl chloride, whereupon 2 g of cetyltrimethylammonium bromide are added to the mixture with vigorous agitation, and the flask is cooled with water so that the temperature of the reaction mass under agitation does not rise above 110°C. Once the exothermic stage is exhausted, the temperature is maintained at 130°C by an external oil bath, for 90 min under agitation.
After cooling, a solid mass is obtained which is taken up with 400 ml of an aqueous solution containing 10% by weight of caustic soda to dissolve the product from the mass. The alkaline solution thus obtained is extracted twice with 500 ml of chloroform. The extract is washed with water and then evaporated to dryness. The residue is crystallised from 96% ethanol.
50.5 g (theoretical value 53.18 g) of 1,4-bispiperonylpiperazine as a paleyellowish white crystals are obtained with a melting point of 155-156°C; the hydrochloride melts with decomposition above 260°C.
Preparation of fipexidum hydrochloride:
106.3 g (0.3 moles) of 1,4-bispiperonylpiperazine are dissolved in 750 ml of hot benzene in a 2,000 ml flask provided with a stirrer and a reflux condenser and 38 g (0.45 moles) of dry, powdered sodium bicarbonate are added. After cooling to ambient temperature, 92.3 g (0.45 moles, corresponding to 63 ml) of the chloride of p-chlorophenoxyacetic acid are added slowly, with agitation, and the mixture is heated under reflux for 7 hours. The benzene is then almost totally recovered by distillation at atmospheric pressure and the residue is evaporated to dryness under vacuum. The solid residue thus obtained is taken up with 400 ml of aqueous solution at 10% sodium hydroxide (1 mole) and the alkaline liquid phase is extracted twice with 600 ml of chloroform. The chloroform extracts are joined together and washed with a little water and then agitated vigorously with a solution of 200 ml of concentrated hydrochloric acid in 300 ml of water. An abundant white precipitate is obtained. After filtration under vacuum, the precipitate is treated with boiling ethanol; the 1-((p-chlorophenoxy)acetyl)-4-piperonylpiperazine hydrochloride (fipexide hydrochloride) passes into solution while the dihydrochloride of hydrochloric acid remains undissolved and is separated by filtration while hot. The alcoholic filtrate is cooled, with consequent slow crystallization of the fipexide hydrochloride. 70.2 g of the product are obtainedwith a yield of 55%; melting point is (in Kofler) 228-230°C.

brand name

Attenil 30 conf. 20 mg;Fipexitum;Fipexium;Vigilor 200 mg cpr msfp.

Therapeutic Function

Antidepressant, Psychostimulant

World Health Organization (WHO)

Fipexide, a stimulant of the central nervous system, was introduced in 1973 for the treatment of depression and memory defects. Following its association with hepatic and hemopoietic disorders, particularly in children, the drug was withdrawn in France. Although not widely marketed, it may still remain registered elsewhere.