SU40981A1 - Method for producing apomorphine - Google Patents

Description

A common method for producing apomorphine is that morphine is heated with concentrated hydrochloric acid in an autoclave at 140-150 for 2 to 3 hours. The acidic solution is neutralized with soda and the base of the apomorphine is extracted with ether. Hydrated apomorphine is precipitated from the ethereal solution with hydrochloric acid. No literature is indicated. When checking out the filers of this method, low and fluctuating outputs were obtained. The solutions, when neutralized with soda, turned green very quickly and the apomorphine was not sufficiently pure.

Much more convenient is the method chosen by the authors for producing apomorphine by heating morphine with phosphoric acid while simultaneously passing hydrochloric acid gas. The preparation is carried out in an open vessel, and thus no acid-resistant autoclave is required. 50 g of morphic hydrochloric acid or base and 500 g of technical phosphoric acid beats are charged to a round bottom flask. at. 1.76. A dry gaseous hydrochloric acid is passed through a tube going to the bottom during the whole heating time. Heating is carried out in an oil bath at a temperature of 145-150 ° for 1 hour.

Upon completion of the heating, the reaction mixture is allowed to cool in the same

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950 cm flask cold water and leave until next day. Over time, a resin may stand out. In such a case, the solution is drained and the resin is dissolved by adding some more water.

The resulting solution is salted out with a solution of sodium chloride until the gum evolution stops. The solution is drained from the resin and the latter is dissolved in 1250 cm of warm water (50-60 °). About 200 z of soda is added to the solution drained from the resin, first the resin is precipitated and at the end a suspended precipitate is added. Soda is added until precipitation stops. The solution with the precipitate suspended in it is drained from the resin and the precipitate is sucked off, after which it is attached to the resin and dissolved together in warm water. The total water to dissolve the resin and sediment is about 750 cm. The solutions of both resins (after salting out with salt and neutralizing with soda) are poured together (total volume 2 liters) and neutralized with sodium sulfite, which is about 100. At the same time, a grayish amorphous sediment is isolated, it is extracted 10-15 times, taking 2 liters of ether each time (until complete extraction). Each stretch was vigorously shaken in a can of 100 c Vi N hydrochloric acid until cessation of precipitation of hydrochloric acid apomorphine was stopped.

and it is sucked off. The ester goes for re-extraction, and the hydrochloric liquor is used for the subsequent extraction from the ether extracts of apomorphine. In this way, about / 7 g of pure hydrochloric acid apomorphine is obtained, which does not require further purification. At the end of all extractions, residues of apomorphine are extracted from the hydrochloric acid of the mother liquor, salting it first with salt and then with soda, but not reducing the reaction to alkaline. The solution is drained, the remaining resin is dissolved in water, neutralized with sulphite and recovered with ether. From the ether extract by shaking with a small amount of hydrochloric acid, about 1.5 i more hydrochloric acid apomorphine is obtained. But this portion is no longer obtained immediately in pure form, but is purified by recrystallization from water with acidified hydrochloric acid.

Total yield 18 g 40 / oh of pure apomorphine hydrochloride.

The subject matter of the invention.

The method of obtaining apomorphins by heating morphine with acids, characterized in that morphine is heated with phosphoric acid at a temperature of 145-150 ° and hydrogen chloride gas is passed through the solution at the same time, then cooled, salted out the resin by adding salt to the solution first, and then soda, until the precipitation stops, after which the precipitated gums and precipitate are dissolved in water, the solution is neutralized with sulphite until the precipitate of apomorphine is completely separated, which is extracted with ether.