SU490281A3 - The method of obtaining-substituted phenoxyacetic acids and their derivatives - Google Patents

Description

i-; ic 1, Pli and X are the above;

Y is a carboxyl residue;

subjected to decarboxylation at a temperature that ensures the elimination of carbon dioxide in the presence of an inert solvent, for example pyridium, followed by isolation of the target product or its conversion into solv, ester or amide by known methods.

In the resulting compounds, free carboxyl, ester and amide groups can be converted into each other by known methods, as well as the salts of these compounds can be obtained.

Acids in the form of their salts with bases are obtained by exchange reaction with the corresponding basic reagents. First of all, therapeutically useful salts with bases are sought, such as salts with organic amines or metal salts. Alkali or alkaline earth metal salts, for example, sodium, potassium, magnesium or calcium salts, are primarily used as metal salts. Free acids can be isolated from salts in a known manner, for example, by treating their acidic reagents. Target products with the main character can be obtained both in free form and in the form of their salts, for example, with such acids as hydrohalic acids, sulfuric, phosphoric, nitric, chloric, aliphatic, alicyclic, aromatic or heterocyclic carboxylic or sulfoic acids, or an anthracite. , acetic acid, nropionic acid, succinic acid, glycolic acid, lactic acid, blocky, tartaric acid, citric acid, ascorbic acid, maleic acid, hydroxymaleic acid, or pyruvic acid; phenylacetic, benzoic, l-aminobenzoic, anthraniline, oxybenzoic, salicylic, or p-aminosalicylic, embonic, methanesulfonic, ethanesulfonic, hydroxyethane sulfonic, ethylene sulfonic acid; halobenzenesulfonyl a, toluenesulfonic, naphthalenesulfonopa acid or sulfanilov; methionine or tryptophan, lick or arginine.

By converting the target compounds into salts and inverse, these substances can be purified.

According to the invention, products containing asymmetric carbon atoms are obtained, i.e., new compounds in the form of ontic antinodes, racemates or mixtures of isomers (for example, mixtures of racemates).

The resulting mixtures of isomers (mixtures of racemates) can be divided into both stereoisomeric (diastereomeric) pure isomers (for example, racemates) by known methods, for example, chromatography and / or fractional crystallization, based on the physicochemical differences of the components. In addition, the racemates obtained can be divided into optical antipodes by well-known methods, for example, by recrystallization from an optically active solvent using microorganisms or by reacting the free carboxylic acid with an optically active base to form salts with the racemic compound, and separating the salts thus obtained, panrimer, into the basis of their different solubility, in diastereomers; of these it is necessary to free the antipodes by the action of the proper means.

A preferred optically active osovay for isolating the more effective antipodes is, for example, the L-form of cinchonin.

The resulting racemates of the basic compounds can be further divided into optical antipodes, subjecting the racemic compound to interaction with an optically active acid that forms salts with it, and the salts thus obtained are divided into diastereomers, for example, on the basis of their different solubility. From the diastereomers, the antipodes can be further released by exposure to the proper means. Especially accepted optically active acids are D- and

L-forms of tartaric, di-o-tolilvinna, block, almond, camphorsulfonic or quinic acids.

Example 1. 6.0 g of (cyclohexenyl) -phenoxy} -sb-n-pentylmalonic acid is heated in 100 ml of pyridine until boiling - until the formation of carbonic acid is stopped. Then, a large portion of niridine is placed under vacuum, 200 ml of water is added to the residue, brought to acidic reaction with concentrated hydrochloric acid and extracted 3 times with 200 ml of methylene chloride. The organic phases are washed with 2 times 200 ml of water until neutral, the pad is dried with sodium sulphate and evaporated under vacuum to dryness. After

recrystallization from the non-net ether, obtain (cyclohexen-1-yl) -phenoxy-heptanoic acid of the formula

v / l

./- oss

so nl 78-80 ° C; yield 42% (from theory). According to the proposed method, the following compounds are preferably obtained:

(cyclohexen-1-yl) -phenoxy-c-octanoic acid; m.p. 70-7GS;

(cyclohexen-1-yl) phenoxy - n - nonanoic acid; m.p. 61-63 ° C;

(cyclohexen-1-yl) -phenoxy) -n-dodecanoic acid; m.p. 70-72 ° C;

(cyclohexen-1-yl) -phenoxy-n-undecanoic acid; m.p. 70-73 ° C; (cycloocten-1-yl) -phenoxy - c - gentanoic acid; so nl 57-60 ° C; m.p. 185–188 ° C (0.04 mmHg);

(cycloocten-1-yl) -phenoxy-n-octanoic acid; m.p. 55-57 ° C; (cycloocten-1-yl) -phenoxy-n-decionic acid; m.p. 216-219 ° C (0.05 mm Hg. Art.);

(cycloocten-1-yl) -phenoxy-n-dodecanoic acid; m.p. 45-48 ° C;

a-p-cyclohexen-1-yl) -phenoxy - // - decapore, cc) acid; m.p. 75-78 ° C;

(cyclooct-11-1-yl) feioxy-n-tetradecanoic acid; a- / g-cycloocten-1-yl) -phenoxy-n-tetradecanoic acid ethyl ester;

iso-iroimylamide (cyclohexei-1-yl) -feioxy-n-heptaic acid; m.p. 86-88 ° C.

Subject invention

The method of obtaining a-substituted phenoxy x. X acids and their derivatives of general formula I

R, -CH-X

R-Ph-Ogde H-cycloalken-1-yl; RI is alkyl C5-Ci2,

predominantly

With Ci2,

Ph - phenylene;

X is a carboxyl, ester or amide group, characterized in that the compounds of general formula II

RI

R-Ph-OC

II

Have

where R, RI, Ph and X have

the above values;

Y is a carboxyl residue, is decarboxylated at a temperature that ensures carbon dioxide detachment in the presence of an inert solvent, for example pyridine, followed by isolation of the target product or its conversion into salt, ester or amide by known techniques.