CH668066A5 - New alkyl 4-alkoxy-2-oxo-3 -pyrroline-1-acetate cpds. - Google Patents

Abstract

Alkyl 4-alkoxy-2-oxo-3-pyrroline-1 -acetates of formula (I) are new: (where R1 = Me or Et; R2 = 1-4C alkyl or benzyl.

Description

       

  
 



   DESCRIPTION



   The 4-alkoxy-3-pyrrolin-2-one-1-yl -acetic acid alkyl esters are valuable intermediates for the production of the ce-rebral active 4-hydroxy-2-oxo-pyrrolidin-1-yl-acetamide.



   Some methods are known for the preparation of the active ingredient, but all have the disadvantage of unprofitability because of poor yields or expensive starting materials.



   The task was therefore to develop methods that avoid these disadvantages.



   An essential part of the object could be achieved with the present method according to claim 1, which allows starting from 4-halo-3 - (C1-C2) alkoxy-2-ebutene acid C1-C4-alkyl ester by reaction with glycine Cl-C4-alkyl or benzyl ester or its hydrohalide in the presence of a base to convert the desired 4-alkoxy-3-pyrrolin-2-one-1-yl-acetic acid ester.



   The 4-halo-3 - (C1-C2) alkoxy-2-E-butenoic acid C 1 -C 4 -alkyl ester can be prepared in a manner known from the literature, e.g. according to Köhler, dissertation University of Bayreuth 1985, from 4-haloacetoacetic ester.



   The reaction is conveniently carried out in the presence of weak inorganic bases or tert. aliphatic amines carried out as bases. Particularly preferred representatives of the weak inorganic bases are e.g. Sodium acetate, potassium carbonate or potassium hydrogen carbonate.



  As a suitable representative of a tert. aliphatic amine, triethylamine can be used.



   It is also advantageous to carry out the reaction in a solvent. Aprotic or protic solvents with high polarity are expediently used for this purpose.



   Suitable representatives are e.g. Acetonitrile, propionitrile, butyronitrile, diethylene glycol monomethyl ether, diethylene glycol dimethyl ether, N, N'-dimethylformamide or N, N'-dimethylacetamide.



   The glycine-C1-C4-alkyl or benzyl ester is expediently used in an amount of 1 to 4 moles, preferably 1.25 to 2 moles, per mole of haloalkoxybutonic acid ester.



   The hydrohalide, preferably the hydrochloride of the glycine alkyl ester, is often used. Then it is convenient to treat with the haloalkoxybutenic acid ester by treating with a base such as e.g.



  a trialkylamine, preferably triethylamine, or with an alkali methylate, such as sodium methylate, to convert the glycinalkyl ester hydrohalide into the free glycinalkyl ester.



   The reaction temperature is appropriately chosen between 60 and 120 C.



   If the boiling point of the solvent allows it (e.g. acetonitrile), you can work at the reflux temperature.



   After the reaction has ended, the product is worked up by extraction and optionally by subsequent recrystallization.



   With these methods according to the invention, yields are achieved which generally exceed 80%.



   The contents of the products obtained are usually higher than 95%.



   Example 4-methoxy-3-pyrrolin-2-one -I-yl-acetic acid zentyl from 4-chloro-3-methoxy-buten-2-E-acidic acid methyl ester
A suspension of 6.5 g (0.052 mol) of glycine methyl ester hydrochloride in 30 ml of acetonitrile was mixed with a solution of 5.3 g of triethylamine in 10 ml of acetonitrile.

 

  The mixture was heated to reflux and 2.1 g of anhydrous sodium acetate were added. A solution of 4.4 g (0.025 mol) of 4-chloro-3-methoxybutene-2-E-acidic acid methyl ester (content (GC): 95.2%) and 20 ml of acetonitrile was then added dropwise within 30 minutes. The mixture was allowed to stir under reflux for 4.5 hours. The reaction solution was then cooled to 0 ° C., the precipitated solid was filtered off and the filtrate was concentrated on a rotary evaporator. The residue was taken up in 100 ml of ice water, acidified with 6.0 g of 32% hydrochloric acid and extracted five times with 100 ml of methylene chloride organic solution was dried over Na2SO4 and evaporated. The residue was recrystallized from 30 ml of carbon tetrachloride. 4.0 g of white, crystalline product of melting point: 105 to 107 C (GC content: 96%) were obtained. Yield: 81.5% .


    

Claims (4)

 PATENT CLAIMS 1. Process for the preparation of 4-alkoxy-3-pyrrolin-2on-l-yl-acetic acid ester of the formula EMI1.1  where R1 = C1-C2-alkyl and R2 = C1-C4-alkyl or benzyl. characterized in that a 4-halogen 3- (C, -C,) - alkoxy-2-E-butenoic acid C1-C4-alkyl ester with a glycine-C1-C4-alkyl or -benzyl ester or its hydrohalide converted to the end product in the presence of a base.    2. The method according to claim 1, characterized in that weak organic bases or tertiary aliphatic amines are used as the base.  3. The method according to claims 1 and 2, characterized in that the reaction is carried out in an aprotic or protic solvent with high polarity.  4. The method according to claims 1, 2 and 3, characterized in that one carries out the reaction at temperatures between 60 and 120 C.