2-(4-butoxyphenoxy)-N-(2,5-diethoxyphenyl)-N-[2-(diethylamino)ethyl]acetamide monohydrochloride

Suplexedil,Hepatrol,France,1974

420 grams of 2,5-diethoxy aniline are dissolved in 4 liters of dichloroethane and 230 grams of triethylamine are added. The mixture is heated, while stirring, with 845 grams of 4-butoxy phenoxy acetyl chloride. The temperature increases towards 40°C. The mixture is then heated for 2 hours at 80°C. After cooling the product is washed with normal hydrochloric acid, then with water, then with normal sodium carbonate and finally with water.
The organic phase is dried over sodium sulfate, filtered, the dichloroethane is evaporated off and the residue is crystallized from ethyl alcohol (95%). The product is dried in the oven and there is thus obtained about 800 grams (yield 90%) of the N-(2,5-diethoxyphenyl)-4-butoxy phenoxy acetamide, MP 101°C.
A vessel provided with a mechanical agitator, a thermometer and a refrigerant, is charged with 49.2 grams of sodamide (90%) in suspension in 300 ml of anhydrous toluene, and a solution of 465 grams of amide obtained as above in 2 liters of anhydrous toluene. The solution is poured in, little by little during 1.5 hours with slight warming. The mixture is maintained for 1 hour at 80°C during which ammonia is evolved. It is cooled to 45°C, there is added, in a single quantity, 170 grams of 2-diethyl-amino-1-chloroethane and the temperature is raised slowly to 100°C and is maintained there for 10 hours.
The mixture is cooled, the organic phase washed with water and dried over sodium sulfate. The toluene is evaporated and the residue taken up in 2 liters of normal acetic acid, with cooling. It is allowed to crystallize in the cold, filtered to remove the insoluble portion and the base precipitated from the filtrate by the addition of sodium carbonate; this is extracted with dichloroethane and the organic phase dried over sodium sulfate. After evaporation of the solvent an oil is distilled, BP 225° to 230°C/0.1 mm, weight 340 grams, yield 58%. The hydrochloride prepared by the action of gaseous hydrogen chloride on this oil in ethyl ether melts at 140°C.

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