AT238187B - Process for the preparation of new pyrrolidine compounds - Google Patents

Description

  

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  Process for the preparation of new pyrrolidine compounds
The invention relates to a process for the preparation of new pyrrolidine compounds and their acid addition salts. In particular, the invention relates to a method of making
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 the alkali hydroxides, alkali alkoxides and alkali metals can be used. The reaction is most conveniently carried out in a high-boiling organic solvent (1500C or above) such as diethylene glycol, octyl alcohol, triethanolamine. Ethers of diethylene glycol u. Like., performed. Lower-boiling organic solvents such as ethanol or n-propanol. can also be used, but the reaction temperature requires a closed vessel when using such solvents.

   The reaction is carried out at a temperature of about 150 to 210.degree. The hydrazone or semicarbazone starting material can be formed in situ from hydrazine or semicarbazide and the corresponding 4-ketopyrrolidine compound. Another embodiment is to simply raise a mixture of the 4-ketopyrrolidine compound with hydrazine and the alkaline catalyst to the reaction temperature instead of first working at a lower temperature to form the hydrazone and then increasing the reaction temperature.



   The 4-ketopyrrolidine compounds and their hydrazone and semicarbazone derivatives used as starting materials in the above process can be prepared by reacting the 4-keto group with ethylene glycol, reducing the 2-keto group in the condensation product with lithium aluminum hydride and hydrolyzing the reduction product with mineral acid. The hydrazone can be produced from the 4-ketopyrrolidine by reaction with hydrazine, and the semicarbazone by reaction of the 4-ketopyrrolidine with semicarbazide.



   The procedure according to the invention is applicable to both racemic and separate, optically active forms. In those cases where optically active products are desired, they can be obtained either by using optically active starting materials or by using optically inactive starting materials in the process of the invention and separating the pyrrolidine compound thus obtained by fractional crystallization of a salt with an optically active acid. Some examples of optically active acids useful for this purpose are α-tartaric acid, dibenzoyl-α-tartaric acid, α-camphor sulfonic acid, α-mandelic acid, di-p-toluoyl-α-tartaric acid and the corresponding 1-isomers.

   The salt formation and fractional crystallization of the optical isomers is preferably carried out in a lower aliphatic alcohol such as isopropanol, absolute ethanol and the like. Like. Performed. After the separation of the salts of pyrrolidine with an optically active acid, each of the separated salts can be separately treated with an alkaline reactant such as alkali hydroxide, alkaline earth hydroxide, alkali carbonate, alkali alkoxide, ammonia, alkali bicarbonate, an organic tertiary amine or the like to obtain the free base of the individual optical isomers of the pyrrolidine compound.



   The invention is illustrated by the following examples.



   Example 1: 149 gl, 5-dimethyl-3- (m-methoxyphenyl) -3-propyl-4-pyrrolidone hydrochloride in a small amount of water is added to 250 g of potassium hydroxide, 150 ml of 85% hydrazine hydrate and 1200 ml of diethylene glycol and the mixture 2 hunter reflux held. The water is removed by distillation and the temperature of the residue is increased to 2000C. The mixture obtained in this way is heated under reflux for 6 h, cooled, diluted with water and extracted with ether.

   The ether
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The 1,5-dimethyl-3- (m-methoxyphenyl) -3-propyl-4-pyrrolidone used as starting material can be prepared as follows: 184.5 g of m-methoxyphenylacetyl chloride and 40 g of sodium hydroxide in

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