CH242156A - Process for the preparation of a, y-dioxy-B, B-dimethyl-butyric acid- (3 ', 4'-dioxy-butyl) -amide. - Google Patents

Description

  

  Process for the preparation of a, Y-diogy-f, ss-dimethyl-butyric acid- (3 ', 4'-diogy-butyl) -amide. In Swiss patents Nos. 227706, 233770 and 239703, methods are used to obtain therapeutically valuable oxyalkylamides of a, .y-dioxy-ss "f-dimethyl butyric acid by reacting d (-) - a-oxy-ss , ss-dimethyl-y-butyrolactone described with oxyalkylamines.



  It has now been found that very pure 3,4-dioxy-butylamide of the <I> a, 1- </I> dioxy-ss, ss-dimethyl-butyric acid can be obtained in a particularly convenient manner by adding 3, 4- (Dimethyl-methylen-dioxy) -butyl-amine with a-oxy-ss, ss-dimethyl-y-butyrolactone and the resulting 3,4- (dimethyl-methylen-dioxy) -butylamide of a, y-dioxy - ss,

  ss - dimethyl - butyric acid is subjected to a mild, acidic hydrolysis. The implementation proceeds according to the following scheme:

    
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    In this reaction it is surprising that it is possible to split off the acetone residue from the condensation product without dissolving the amide bond, because both pantothenic acid and the oxyalkylamides of α, γ-dioxy- ss, ß-dimethylbutyric acid are extremely light compared to other acid amides saponifiable. The optical activity is not influenced by the hydrolysis.



  The 3,4- (dimethyl-methylen-dioxy) -butylamine (II) required as starting material can be prepared as follows: 8-oxy-y-valerolactone (Leuchs and coworkers, reports of the German Chemical Society, Vol. 40 [ 1907] p. 801; vol. 42 [1909] p. 1228;

    Winterfeld, Arch. Pharm> Vol. 277 [1939] p. 227) is converted into 4,5-dioxy-valeric acid amide by standing for two days in 6 times the amount at 0 using methanol saturated with dry NH3, which is a colorless, thick <B> 01 </B> is obtained. This is then dissolved in about 100 parts of dry acetone; a little dry hydrochloric acid gas is then introduced until the solution reacts acidic against the Congo.

   After standing for a day, it is shaken with a little solid pot ash, filtered and evaporated. The 3,4- (dimethyl-methylene-dioxy) -valeric acid amide remaining as residue distills in vacuo at 0.1 mm below 125 and crystallizes from acetone-ether in colorless platelets with a melting point of 92.

   Hofmann's degradation of this amide provides the base (II) we are looking for, which boils in a vacuum of 11 mm at 74-75 as an easily mobile, colorless liquid and easily attracts CO 2 and water from the air. It gives a picrate melting at 157-158.



  For condensation, the 3,4-dimethylmethylene-dioxy) -butylamine is expediently reacted with the equimolar amount of a-oxy-ss, ss-dimethyl-y-butyrolactone, which is advantageously done in an inert solvent in both components are soluble. The reaction takes place after about 24 hours at room temperature and can be accelerated by heating.

   The 3,4- (dimethylmethylene-dio @ xy) -butylamide of α, γ-dioxy- ss, ß-dimethyl-butyric acid thus obtained forms a colorless oil which can be distilled in a high vacuum without stopping. The compound distills under a pressure of 0.1 mm at a bath temperature of about 130.



  The a, y-dioxy-ss, ss-dimethyl-butyric acid- 3 ', 4'- (dimethyl-methylene) - dio.xy) -butylamide (III) yields the 3,4-dioxy with mild, acidic hydrolysis butylamide of da, y-dioxy-ss, ss-dimethyl-butyric acid (IV) as a colorless, hygroscopic., very viscous <B> 01, </B> whose analysis values match the formula CloH "0 ;; N and that Cannot be distilled in full, even in a vacuum.

   It is identical to the compound described in Swiss Patent No. 239703. When tested on rats, the process product has all the physiological properties of pantothenic acid. It is also valuable as an intermediate.



       Example: 2 parts by weight of d, l-dimethyl-methylene-3,4-dioxy-butylamine and 1.7 parts by weight of <B> d (-) </B> - a - oxy - ss., Ss - dimethyl - y - butyrolactone are dissolved in 12 parts by weight of anhydrous benzene and the solution refluxed for one hour with exclusion of moisture. The solution is then brought to dryness by evaporation in vacuo.



  No further purification is required for further processing, although it is possible to distill the compound at 0.1 mm pressure. The. When analyzed, the distillation product gives values for carbon, hydrogen and nitrogen that are consistent with theory.



  7 parts by weight of the crude condensation product are dissolved in 50 parts by volume n / 10 sulfuric acid and left to stand at 18. Based on the determination of the acetone split off, it can be demonstrated that the saponification is complete under these conditions after 30 minutes.

   The solution is neutralized by stirring in excess freshly precipitated barium carbonate and filtered through a suction filter covered with barium carbonate and a little boiled charcoal. The filtrate contains the sought d (+) - 2,4-dioxy-3,3-dimethyl-butyric acid- (3 ', 4'-dioxybutyl) -amide, which remains when the solution is narrowed in a vacuum. It is identical to the connection described in Swiss patent no. 239703.

 

Claims (1)

PATENT CLAIM: Process for the preparation of a, y-dioxy- ss, ss-dimethyl-butyric acid (3 ', 4'-dioxy-butyl) amide, characterized in that 3,4- (dimethyl-methylene-dioxy) -butylamine is reacted with a-oxy-ss, ss-dimethyl-y-butyrolactone and the reaction product is subjected to mild, acidic hydrolysis.