CS258279B1 - Process for the preparation of methyl 2- (tetrahydrofurfuryl) -3- (1-naphthyl) propionate - Google Patents

Abstract

The solution falls into the field of drug synthesis. Its subject is a method for preparing methyl ester of 2-(tetrahydrofurfuryl)-3-(1-naphthyl)propionic acid of formula I, which is an intermediate in the production of drugs, especially substances with cerebral vasodilating activity. The method for preparing the substance of formula I according to the solution consists in the reaction of sodium salt of 2-(tetrahydrofurfuryl)-3-(1-naphthyl)propionic acid with dimethyl sulfate in boiling methanol. The ester of formula I, as well as the starting acid, are a mixture of two racemates.

Description

The present invention relates to a process for the preparation of 2- (tetrahydrofurfuryl) -3- (1-naphthyl) propionic acid methyl ester of formula X

The compound of formula I is an intermediate in the manufacture of medicaments, in particular substances with vasodilating, spasmolytic and locally anesthetic activity. Representative of this class of drugs is the naphthyrdrofuryl, i.e. 2- (tetrahydrofurfuryl) -3- (1-naphthyl) propionic acid 2-diethylaminoethyl ester, used in the form of hydrogen oxalate as an oerebral vasodilator in gerontology, especially gerontopsychiatry.

the compound of formula I is mentioned in the publication (Szarvasi E. et al .: Bull. Soc. Chim. Fr. 1963,

181) and reported to have been prepared in 70% yield from 2- (tetrahydrofurfuryl) -3- (1-naphthyl) propionic acid II

(ID by esterification with methanol to sulfuric acid catalysis. Both the starting acid of formula II and the ester of formula I are due to the presence of two chiral centers in the molecule of a mixture of two racemates. ° C / 133 Pa.

It has now been found that a more preferred method of esterifying the acid of formula II is to react the sodium salt of the acid of formula II with dimethyl sulfate in methanol. A solution of the sodium salt of the acid of formula II in methanol is obtained by reacting the free acid with an equivalent of a solution of sodium methoxide in methanol. The esterification itself takes place at the boiling point of the mixture. If the pure acid of the formula II obtained by thermal decarboxylation of crystalline 1- (tetrahydro-2-furyl) -3- (1-naphthyl) propane-2,2-dicarboxylic acid is used as starting material, the methyl ester is obtained as pure residue as a residue, whereas it does not need to be distilled for further use. According to gas chromatography, the product thus obtained contains 95% of the desired stereoisomeric mixture. According to high pressure liquid chromatography, this mixture contains 35% of racemates A and 65% of racemates B. The novel process for the preparation of the ester of formula I is the object of the present invention.

The following example is merely illustrative of the possibilities of the invention and is not intended to exhaustively describe all possibilities of the invention.

Example

Sodium (1.8 g) was dissolved in 20 ml of methanol, and a solution of 19.6 g of 2- (tetrahydrofurfuryl) -3- (1-naphthyl) propionic acid (II) (a stereoisomeric mixture) was added with stirring to the bubbled sodium methoxide solution. was obtained by thermal decarboxylation of crystalline 1- (tetrahydro-2-furyl) -3- (1-naphthyl) propane-2,2-dicarboxylic acid in 20 ml of methanol, and a solution of 9.7 was added dropwise at 40 ° C over 1 h. g of dimethyl sulphate in 10 ml of methanol, the mixture is stirred at 50 DEG C. for 2 h, 2.7 g of dimethyl sulphate are added and the mixture is refluxed for 2 h. The methanol is distilled off at atmospheric pressure, the residue is diluted with chloroform. 10% sodium bicarbonate solution and water and dried over sodium sulfate The chloroform was then distilled off completely under reduced pressure, and the residue (20.3 g, 97%) was a crude product which could be used as such for further reactions. sample distils, tv 176 to 180 ° C / 67 Pa, which is in good agreement with the stated literary value.

Claims (1)

SUBJECT OF THE INVENTION A process for the preparation of 2- (tetrahydrofurfuryl) -3- (1-naphthyl) propionic acid methyl ester of the formula I characterized by reacting 2- (4-tetrahydrofurfuryl) -3- (1-naphthyl) propionic acid sodium salt with dimethylsulfate in boiling methanol, a solution of the sodium salt of said acid in methanol is prepared by reacting the free acid with an equivalent amount of sodium methoxide in methanol.