SU793380A3 - Method of preparing substituted indanacetic acids or their salts, or their esters - Google Patents

Description

(54) METHOD FOR OBTAINING SUBSTITUTED INDANEACIC ACIDS OR THEIR SALTS OR THEIR ETHERS

one

The invention relates to a process for the preparation of substituted indan acetic acids or their salts or esters, which can be used as phi31 (logically active compounds for pharmaceutical preparations.

Various substituted indancarboxylic acids are known, for example, phenylindicarboxylic acids 11, or substituted indancarboxylic acids of the general formula

t c-soon

where R is alkyl With,

R 2 is hydrogen or alkyl With PJ

or the general formula

COOZ

where R is phenyl;

Z is alkyl.

Some of these compounds have physiological activity.

The aim of the invention is the synthesis of new substituted indan acetic acids, which can expand the range of physiologically active compounds.

This is achieved by a process for the preparation of substituted indan acetic acids or their salts, or their esters of general formula I

TO/

HI

 - alkyl

Where

il, hydrogen, methyl, ethyl;

 R4 is hydrogen, methyl;

Ry - hydrogen, alkyl

chlorine;

Claims (3)

 R is hydrogen, methyl, by hydrogenation with hydrogen at a temperature in a solvent in the presence of platinum oxide and a strong mineral acid of compounds of general formula II where R., R, R ,, R, f (-j are the indicated values, X is hydroxyl. with Y — hydrogen or X and Y — together represent oxygen or a methylene group. It is advisable to use sulfuric or perchlorogne as a strong mineral acid, and glacial acetic acid, methanol, ethanol as a solvent. Example 1. A solution containing 15 g ci-hydroxy-2-isopropyl-c-methyl-5-indan acetic acid (acid A lower number of 201.8 mg KOH / G, mol 248.32) in 300 ml of glacial acetic acid and 4 ml of 70% perchloric acid is hydrogenated onto platinum oxide (+ 4) in a quantity of 400 mg with temperature and stirring for 15 hours. Then the solution is filtered, 6 g of CH COONa (anhydrous) x are added and the solvent is distilled off. The residue is extracted with ether, the separated ether extract is washed with water, dried with sodium sulfate, filtered and concentrated by evaporation. The target 2-isopropyl-c-methyl-5-indan acetic acid (38% yield) is purified by chromatography on silica gel and recrystallized from hexane. Get the product with so pl. 83-8b ° C, acid number 215 mg KOH / G, mol.v. 232.3 By treating 2-amino-2 hydroxymethyl propane-1,3-diol of the indicated acid, (1,3-dioxy-2-hydroxymethyl-2-propyl) al / 2-isopropyl-o-methyl-B-indanucene unyl salt is obtained. acid, which crystallizes from methanol (sulfuric ether with a melting point of 140-141 ° C). Example 2. The solution, sbber1DI 1.7 g of 2-isopropyl-c (α-methylene-5-indan acetic acid (acidic 217.6 mg con / g; mol. 230.30) in 300 ml of ethanol, is hydrogenated in the presence of 50 mg of platinum oxide (+4) with stirring and a temperature of 20-25 ° C. After filtering off the catalyst, the solvent is distilled off and the remaining oil is chromatographed to give 2-isopropyl-s-methyl-5-indan acetic acid with mp 83-86 s, acid number 215.7 Mg con / g; mol 232.32. Analogously to Example 1, from the corresponding starting materials are obtained: 2-ethyl-c11-methyl 5-indan acetic acid, its ammonium salt mp 182184 s, acid number of acid 229.5 mg con / g; 2-ethyl-4,7, ci-trimethyl-5-indan acetic acid with mp 98-100 c. Example 3. Solution containing 5.2 g of methyl ester of 2-ethyl-6-chloro-2-methyl-bg-oxo-5-indan-acetic acid in 100 ml of methanol and 10 ml of sulfuric acid, hydrogenated in the presence of platinum oxide (+4) at a temperature of 45 ° C, pressure 4 MPa and stirring. After absorbing the theoretical amount of hydrogen, the catalyst is filtered off, the solution is diluted with 5% sodium bicarbonate solution and extracted with ethyl ether. The extract is washed with water, dried over sodium sulfate and evaporated. Purification of the target methyl ester 2-ethyl-b-chloro-2-methyl-5-indan acetic acid is carried out by chromatography on silica gel (chloroform), b.p. -145 ° C / 0.01 mm Hg Similarly, receive the ethyl ester of 2-ethyl-5-indanoacetic acid with so Kip. 102106 ° C / 0, 01 mm Hg Methyl ester of 2-ethyl-2, (- dimethyl-5-indan acetic acid with BP. 138140 C / 0, 3 mm Hg. (1,3-dioxy-2-hydroxymethyl-2-propyl) ammonium salt 2 , 2 diethyl-5-indan acetic acid with mp 11b-119 ° C. Claim 1. The method of producing substituted indan acetic acids or their salts or their esters of general formula I Rl Hit al KIL C-Cs ,, R, is hydrogen , methyl, ethyl, and hydrogen, methyl; RJ is hydrogen, methyl, chlorine; and R -, is hydrogen, methyl, characterized in that the compounds of the general formula I G XY., where R, R, 2, R ", R, Rg, the indicated values; X is hydroxyl, Y is hydrogen and X and Y together represent oxygen or etilenovuyu group, is hydrogenated with hydrogen at a temperature in rastvoritel51 medium in the presence of platinum oxide (4) and a strong mineral acid followed by isolation of the desired product in the form of acid, salt or ester. 2. The method according to claim 1, characterized in that glacial acetic acid or ethanol or methanol is used as a solvent. 3. The method according to paragraphs. 1 and 2, about tl and the fact that sulfuric or perchloric acid is used as a strong mineral acid. Sources of information taken into account in the examination. 1. US patent No. 5523134, cl. 260-515, pub. 1970 2 US Patent 3452085 Cl. 260-515, pub. 1969 3. US patent number 3644479 cl. 260-469, published. 1972.