SU408546A1 - The method of obtaining hydrochloride 1 = aminoadamantana - Google Patents

Description

This invention relates to a process for the preparation of 1-aminoadamantane hydrochloride, which is a known physiologically active compound widely used in pharmacology.

A known method for producing 1-aminoadamantane hydrochloride by reacting an excess (more than fourfold) formamide with bromadomantane at the boiling of the reacton mixture in the presence of a significant amount of sulfuric acid (t 195 ° C, reaction time 5 hours). The output of formyl aminoadamantane 83%. The hydrolysis of cfogo (non-recrystallized formylaminoadamantane is carried out in a large amount of ethanol (104 ml per 5.8 5.8 g) in the presence of hydrochloric acid more than 20% for 1 hour. Part of the product is separated by distilling off alcohol (the hydrochloride in it is a good solution e) followed by recrystallization. Yield 70%. However, the duration of the process, not enough high output, high consumption of initial reagents limits the use of this method.

In order to simplify and intensify the process and increase the yield of the target product, a mixture of 1-bromadomamantane and / or 1-chloroadamantane and formamide, taken in a weight ratio of not more than 1: 2,

heated at a temperature of the reaction mixture not higher than 195 ° C, preferably for not more than half an hour. The obtained 1-formylaminoadamantane is hydrolyzed with not more than 20% hydrochloric acid at a temperature not exceeding 110 ° C.

In this case, upon cooling the reaction mixture, a precipitate of the desired product is formed, which is isolated by simple filtration without crystallization.

Example. A mixture consisting of 200 g of 1-bromoamantane and 360 g (320 ml) of formamide is heated at a gradually increasing temperature of 185-195 ° C for 0.5 hour. The cooled reaction mixture was diluted with water, and the precipitate was filtered off. The resulting wet product is hydrolyzed after determining the moisture in it. Obtain 124.5 g (74.7%) of dry product with so pl. 134-138 ° C. After extraction of the filtrate with benzene or ether, another 8-10 g of product can be crawled, so that the total yield of the reaction is 80-81%. The hydrolysis of the obtained 1-formylaminoadamantane is carried out in 370 ml (three times excess by weight) of hydrochloric acid (18–20% hydrochloric acid must be after the suspension of wet 1-formylaminoadamantane in it) and before the mixture is heated. The reaction mixture is heated at a mass temperature of 108-110 ° C (a higher temperature will result in the formation of 1-chloroadamantane) for 0.5 hour. After cooling, the precipitated 1-aminoadamantane hydrochloride is filtered off. Get 92-100 I (70-76%), considering formylamino admantane. For medical needs, the resulting hydrochloride is recrystallized from isopropanol in the presence of activated carbon and is obtained in 75-77% yield (based on 9 g of hydrochloride, 9 ml of isopropanol). After partial distillation, an additional amount of the desired product is obtained from the isopropanol filtrate. The total yield of recrystallized hydrochloride is about 90%, considering the first OCHOBHJTO portion of the crude hydrochloride. After partial distillation of the filtrate of the hydrochloric acid solution and cooling, still crude hydrochloride is obtained, which increases the overall yield of 85-87% ...

With complete distillation of hydrochloric acid, then another 5-7% of product is obtained, which mainly consists of aminoadamantane hydrochloride, but contains a small amount of an unknown compound}} / ktura. To obtain the pure desired product, the dry residue is dissolved in

water and filtered (impurities do not dissolve in water), and the filtrate is evaporated (this operation is not necessary in practice). Similar results are obtained in the case of replacement of bromoamantane with chloradamantane.

Claims (2)

Invention Formula The method of producing 1-aminoadamantane chlorohydrate by the interaction of halo-adamantane and formamide upon heating followed by hydrochloric hydrolysis of 1-formylaminoadamantane and isolation of the target product, characterized in that, in order to stimulate and intensify the process and increase the yield of the target product, a mixture of 1-bromadantane and / or Chloradamantane and formamide, taken at a weight ratio of not more than 1: 2, are heated at a reaction mixture temperature not higher than 195 ° C, and the semi-juicy with 1-formylaminoadamantane is hydrolyzed with not more than 20% salt hydrochloric acid at a temperature not exceeding 110 C. 2. A method according to claim 1, characterized in that the isolation of the target product is carried out by filtering the precipitate from the cooled reaction mixture.