SU648095A3

SU648095A3 - Method of obtaining optically active izomers of oxadiazole derivative

Info

Publication number: SU648095A3
Application number: SU772457091A
Authority: SU
Inventors: Бюре Жан-Пьер; Эрселен Бернар; Амон Жан-Франсуа; Балеа Тражан
Original assignee: Лаборатуар Кассенне (Фирма)
Priority date: 1977-03-09
Filing date: 1977-03-09
Publication date: 1979-02-15

Description

Изобретение относитс к способу получени не описанных ранее в литературе оптически активных изомеров производного оксадиазола формулы IThe invention relates to a method for producing optically active isomers of an oxadiazole derivative of the formula I not previously described in the literature.

// V-l Сн,// V-l CH,

Г 1 vG 1 v

ы -СНг-$-Ш ( -ъ11 -СООНЭтй соединени могут найти применение в медицине.s -CNg - $ - III (-11-COOH This compound may be used in medicine.

Известен способ расщеплени рацематов , заключающийс в том, что на рацемат действуют оптически активным реагентом. При этом получаетс нова пара веществ, не наход ща с друг с другом в отношени х антиподов.A known method for the resolution of racemates is that the racemate is treated with an optically active reagent. In this case, a new pair of substances is obtained that are not with each other in relation to the antipodes.

Известно также применение при расщеплении paцe дачecкиx кислот таких симметрических оснований как бруцин хинин или цинхонин. Наиболее часто употребл емыми растворител ми при расщеплении рецематов вл ютс вода, спирт, ацетон или этилацетат l .It is also known to use such symmetrical bases as brucine quinine or cinchonin in the cleavage of the growth of dacha acids. The most commonly used solvents in the breakdown of a residue are water, alcohol, acetone or ethyl acetate.

Цель изобретени - получение новых оптически активных изомеров производных оксадиазола.The purpose of the invention is to obtain new optically active isomers of oxadiazole derivatives.

Поставленна цель достигаетс описываемым способом получени оптически активных изомеров производного аксадиазола формулы 1, заключающёмс в том, что провод т расщепление рацемата действием оптически активного основани - цинхонина в среде низшего алифатического спирта при температуре кипени реакционной смеси. Образованные оптически активные изомеры кислот могут быть превращены в соли действием минерального или органического основани или в сложные эфиры действием алканола с 1-4 атомами углерода, или действием аминоспир Хта формулыThis goal is achieved by the described method of obtaining optically active isomers of the axadiazole derivative of formula 1, namely, that the racemate is cleaved by the action of the optically active base, tsinhonin, in an environment of lower aliphatic alcohol at the boiling point of the reaction mixture. Formed optically active acid isomers can be converted into salts by the action of a mineral or organic base or into esters by the action of an alkanol with 1-4 carbon atoms, or by the action of amino hydroxyl formula

HO-(CHz)nNHO- (CHz) nN

где X - атом водорода, или алкил, содержащий 1-4 атома углерода.where X is a hydrogen atom, or alkyl containing 1-4 carbon atoms.

Пример 1. Раздвоение рацемической (3-фенил-1,2,4-оксалиазол-5-ил )-метил -тиопропионовой кислоты .Example 1. Bifurcation of racemic (3-phenyl-1,2,4-oxaziazol-5-yl) methyl-thiopropionic acid.

Claims

A mixture consisting of 26.4 g of racemic 2-S (3-phenyl-1, 2,4-oxadiazol-5-yl-methyl-thiopropionic acid, 29.4 g of cinchonine is heated under reflux for 3 hours. and 100 cm of methanol, cooled, evaporated to dryness, the residue was taken up in 100 cm of acetone and left for 48 hours. The precipitate was filtered off with suction and washed with acetone. l cat 75. solution of α-B and hydrochloric acid, extracted with ether, washed with ether for 1 h. with a solution of hydrochloric acid and bodb, dried and evaporated to dryness. The residue is recrystallized from tetrachloride to get 9 g of crystals. oSdg- -, (chloroform). 6} the precipitate obtained above is dissolved in 75 cm3 of acetone and left for 24 hours at 2 ° C, and the filtrate is filtered off with suction. This precipitate is treated with hydrochloric acid as described above and. 8 g of otjjs -10 ° crystals (chloroform) are obtained. The filtrate obtained in item b is evaporated to dryness and the residue is treated with hydrochloric acid, as indicated in item a, and 4 g of cristaeples are obtained, the same as those obtained in item a. d- + 4.7 ° (chloroform). PRI me R

2. Ethyl esters of the double dibasic 2-CS (3-phenyl-l, 2,4-oxydiazol-5-yl) -methyl-tiopropionic acids,.:, ..,.,:;., J. ;;, .:.; Anhydrous hydrochloric acid in 50 cm of ethanol is taken for 15 minutes and then allowed to cool. a) Esterification of levorotating acid. With a stirring and at room temperature for 16 hours a mixture of 1 g of levorotat of the acid of example 1 in 20 cm of hydrochloric acid ethanol prepared above is kept at room temperature for 16 hours, the solvent is evaporated, taken up in ether, washed with water and sodium hydrogen carbonate, dried and evaporated to dryness. The desired ester is obtained, ot-jj-10, 9 (chloroform) b) Esterification of the programing acid. On the basis of about 5 g of the degrading acid obtained in Example 1 according to the above procedure, the target ester e оC + 6.25 (chloroform) is obtained. The invention The method for producing optically active isomers of an oxadiazole derivative of the formula T (K1 "H -CH2 - $ - C-COOH," is that the racemate is cleaved by the action of the optically active base tsonhin in the environment of lower aliphatic alcohol at the boiling point of the reaction mixture. Sources of information received in attention. At the examination. 1. Terentyev A, P ,, Potapov VM Fundamentals of stereochemistry, M., Himi, 1964, p.357,