eprozinol

Originator

Eupneron,Lyocentre,France,1973

Definition

ChEBI: Eprozinol is a benzyl ether.

Manufacturing Process

Stage 1: Preparation of 2-Phenyl-2-Methoxy-Ethyl Bromide - 1.3 mols of tertbutyl hypobromite is added slowly and with agitation to a mixture of 107 grams (1 mol) of vinyl benzene (styrene) and 250 ml of methanol (99%), kept at -10°C. When the addition of the reactant is finished, the mixture is allowed to return to ambient temperature, it is washed in water and dried on anhydrous Na2SO4. Rectification is effected in vacuo in order to obtain a colorless liquid BP12= 113°C, BP2-5=84°C, nD20.6 = 1.5429, yield = 76%.
Stage 2: Preparation of 1-[2-Phenyl-2-Methoxy]-Ethyl-Piperazine - 210 grams of 2-phenyl-2-methoxy-ethyl bromide and 260 grams of anhydrous piperazine are heated for 5 to 6 hours to reflux in 600 ml of ethanol, 500 ml of ethanol is then distilled off and finally the solvent is removed in vacuo. The residue is taken up in 250 ml of benzene and the piperazine hydrobromide is filtered off. The benzene is removed in vacuo. The oily residue is taken up by 450 ml of water and acidification is effected up to pH = 1 by concentrated HCl. The aqueous solution is filtered; the latter is then made alkaline by 50% aqueous NaOH. The liberated base is decanted, the alkaline aqueous solution is washed twice by 150 ml ether. After distillation of the ether, the previously decanted oil is added to the residue and distillation is effected in vacuo. Thus,135 grams of a colorless viscous oil, becoming carbonated in air, is obtained. BP14= 166°C, nD20 =1.5321, yield = 61%.
Stage 3: Preparation of 1-[2-Phenyl-2-Methoxy]-Ethyl-4-[2-Benzoyl-Ethyl]- Piperazine Dihydrochloride -There are heated to reflux and with agitation for 6 hours, 166 grams 1-[2-phenyl-2-methoxy]-ethyl-piperazine, 400 ml ethanol (96°), 260 ml absolute ethanol with 23% HCl gas, 112 grams acetophenone, 32 grams trioxymethylene and 0.8 ml concentrated aqueous HCl. After cooling, the product crystallizes. Recrystallization is effected in ethanol (96°) (1.400 liters for the quantity indicated). 246 grams of a white crystalline powder is thus obtained, slightly soluble in water and alcohol. MP (instant) = 168°C with decomposition, yield 77%.
Stage 4: Preparation of 1-[2-Phenyl-2-Methoxy]-Ethyl-4-[3-Phenyl-3- Hydroxypropyl]-Piperazine Dihydrochloride -In a double-neck flask equipped with a thermometer and a mechanical stirrer, there is placed in suspension in 800 ml of methanol, 233 grams of 1-[2-phenyl-2-methoxy]-ethyl-4-[2- benzoyl-ethyl]-piperazine dihydrochloride (0.55 mol). It is cooled to approximately 5°C, and 46 grams of NaOH pellets dissolved in 80 ml of H2O are added. When the temperature is about 5°C, one addition of 29.2 grams of sodium borohydride in 40 ml H2O is made. The ice-bath is then removed and stirring continued at ambient temperature for 6 hours.
Cooling is effected in the ice-bath while slowly adding concentrated HCl up to a pH of 2, while maintaining the temperature around 5°C. It is filtered and an equal volume of H2O is added. If the solution is cloudy it is washed in ether. It is alkalized by aqueous NaOH (40%), and the oil formed is extracted withether. The ether phase is washed with water saturated with NaCl, then it is dried over anhydrous Na2SO4.
After evaporation of the solvent, a very thick, colorless oil is obtained. This base is dissolved by 200 ml of absolute ethanol and the quantity of HCl to obtain the dihydrochloride is added. It is left for a few hours over ice, dried, washed with approximately 100 ml of anhydrous ether in order to obtain 190 to 195 grams of 1-[2-phenyl-2-methoxy]-ethyl-4-[3-phenyl-3-hydroxy]- propyl-piperazine dihydrochloride after drying at 60°C in vacuo. The yield is 80%. It is recrystallized from absolute ethanol. The product is in the form of white crystalline powder, soluble in water, slightly soluble in alcohol, insoluble in ethyl acetate.

Therapeutic Function

Bronchodilator