SU419029A3 - METHOD FOR OBTAINING TERTIARY AMINO ACIDS OF THEIR SALTS - Google Patents
METHOD FOR OBTAINING TERTIARY AMINO ACIDS OF THEIR SALTSInfo
- Publication number
- SU419029A3 SU419029A3 SU1493628A SU1493628A SU419029A3 SU 419029 A3 SU419029 A3 SU 419029A3 SU 1493628 A SU1493628 A SU 1493628A SU 1493628 A SU1493628 A SU 1493628A SU 419029 A3 SU419029 A3 SU 419029A3
- Authority
- SU
- USSR - Soviet Union
- Prior art keywords
- acid
- ether
- chloro
- ethanol
- sulfuric
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- C07D207/26—2-Pyrrolidones
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- C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
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Description
1one
Изобретение относитс к способу получени Лизиологически активных соединений, которые могут найти применение в фармацевтической практике.This invention relates to a process for the preparation of lysiologically active compounds which can be used in pharmaceutical practice.
Основанный на известной реакции взаимодействи галоидалкилов или алкиламмониевых солей с цианидом щелочного металла с последуюш,им гидролизом нитрилов карбоновых кислот до свободных кислот нредлагаемый снособ получени третичных аминокислот общей формулыBased on the known reaction of reacting haloalkyls or alkylammonium salts with alkali metal cyanide, followed by hydrolysis of nitriles of carboxylic acids to free acids, it is proposed to obtain tertiary amino acids of the general formula
А N-Ph-C-COOHAnd N-Ph-C-COOH
--I--I
RR
где RI - водород, низший алкил; Ro - водород , алкил, циклоалкил, циклоалкил-низший алкил; Ph - замещенный или незамещенный фенилён; А - незамещенный или замещенный на ОКСО-, окси- или алкапоилоксигруппу низший алкилеп, пизщий алкенилен, низщий азаалкилен , низший оксаалкилен или низщий тиаалкилен, причем два гетероатома отделены друг от друга по меньшей мере одним атомом углерода,where RI is hydrogen, lower alkyl; Ro is hydrogen, alkyl, cycloalkyl, cycloalkyl-lower alkyl; Ph is substituted or unsubstituted phenyl; A - unsubstituted or substituted on OXO-, hydroxy- or alkapoyloxy group - lower alkylep, pischy alkenylene, lower azaalkylene, lower oxaalkylene or lower thiaalkylene, with two heteroatoms separated from each other by at least one carbon atom,
или их солей заключаетс в том, что соединение общей формулыor their salts is that the compound of the general formula
R,R,
AjN-ph-c-RAjN-ph-c-R
RVRV
где Ri, R2, Ph п А имеют вышеуказанные значени ;where Ri, R2, Ph p A are as defined above;
Ra - реакционноспособна этерифицировапна в простой или слолсный эфир оксигруппа, например, галоид пли аммониева группа, обрабатывают цианидом щелочного металла, полученный пнтрил кислоты гидролпзуют п выдел ют целевой продукт в виде основани или перевод т его в соль известным способом .Ra is a reactive esterified hydroxyl group or an ester ether, for example, an ammonium halide or an ammonium group, is treated with an alkali metal cyanide, the resulting polyhydric acid is hydrolyzed and the desired product is isolated as a base or converted into a salt in a known manner.
Полученные соеднненп обладают высоко биологической активностью.The resulting compounds have highly biological activity.
Пример 1. Раствор 5 г З-хлор-4-морфолипобензилхлорида в 10 мл диметилсульфоксида прикапывают при перемешивании к суспензии 2,5 г высушенного в вакууме цианида натри в 50 мл днметилсульфоксида, наблюда повышенне температуры до 40°С. Перемешивают 30 мин при 60°С, охлаждают, обрабатывают 250 мл лед пой воды и экстрагируют смесью этилацетат-простой эфир (1:1). После сушки органический экстракт выпаривают в вакууме, перекристаллизовывают остаток из нетроле11ного эфира и получают 3хлор-4-морфолинофенилацетонитрил , т. пл. 124-126°С.Example 1. A solution of 5 g of H-chloro-4-morpholipobenzyl chloride in 10 ml of dimethyl sulfoxide was added dropwise with stirring to a suspension of 2.5 g of sodium cyanide dried in vacuum in 50 ml of dimethyl sulfoxide, and the temperature was increased to 40 ° C. The mixture is stirred at 60 ° C for 30 minutes, cooled, treated with 250 ml of ice-water and extracted with ethyl acetate-ether (1: 1). After drying, the organic extract is evaporated in vacuo, the residue is recrystallized from non-ether ether, and 3-chloro-4-morpholinophenylacetonitrile is obtained, m.p. 124-126 ° C.
Дл синтеза исходного соединени 200 г 4хлор-3-нитробензойной кислоты и 400 мл морфолнна нагревают 5 час при 140°С, выпаривают в вакууме, добавл ют к остатку 4000 мл воды и 1500 мл этанола, подкисл ют смесь 2 н. сол ной кислотой до , отфильтровывают осадок и перекристаллизовывают его из этанола. Получают 4-морфолино-З-нитробензойную кислоту, т. пл. 175-176°С.For the synthesis of the starting compound, 200 g of 4 chloro-3-nitrobenzoic acid and 400 ml of morpholine are heated for 5 hours at 140 ° C, evaporated in vacuo, 4,000 ml of water and 1500 ml of ethanol are added to the residue, the mixture is acidified with 2N. hydrochloric acid before, the precipitate is filtered off and recrystallized from ethanol. Get 4-morpholino-Z-nitrobenzoic acid, so pl. 175-176 ° C.
Смесь 80 г 4-морфолино-З-нитробензойной кислоты, 500 мл метанола и 30 мл концентрированной серной кислоты кип т т 3 час с обратным холодильником, выпаривают в вакууме , обрабатывают остаток водой, подщелачивают гидроокисью натри до слабо щелочной реакции и экстрагируют этилацетатом. Промытый органический экстракт сущат, выпаривают в вакууме, перекристаллизовывают остаток из смеси серный эфир-петролейный эфир и получают метиловый эфир 4-морфолино-З-нитробензойной кислоты, т. пл. 97- 99°С.A mixture of 80 g of 4-morpholino-3-nitrobenzoic acid, 500 ml of methanol and 30 ml of concentrated sulfuric acid is boiled under reflux for 3 hours, evaporated in vacuo, the residue is taken up in water, alkalized with sodium hydroxide to slightly basic reaction and extracted with ethyl acetate. The washed organic extract is dissolved, evaporated in vacuo, the residue is recrystallized from a mixture of sulfuric ester-petroleum ether and 4-morpholino-3-nitrobenzoic acid methyl ester is obtained, mp. 97-99 ° C.
96,5 г метилового эфира 4-морфолино-З-нитробензойной кислоты в 500 мл этанола гидрируют на 5 г 10%-ного осажденного на угле палладиевого катализатора до поглощени теоретического количества водорода (), разбавл ют смесь 500 мл диметилформамида, нагревают до кипени и фильтруют. Фильтрат выпаривают в вакууме до первоначального объема, охлаждают, отфильтровывают осадок и получают метиловый эфир 3-амино-4-морфолинобензойной кислоты, т пл 189- 191°С.96.5 g of 4-morpholino-3-nitrobenzoic acid methyl ester in 500 ml of ethanol is hydrogenated with 5 g of a 10% palladium catalyst precipitated on a carbon to absorb the theoretical amount of hydrogen (), the mixture is diluted with 500 ml of dimethylformamide, heated to boiling and filtered. The filtrate is evaporated in vacuo to the original volume, cooled, the precipitate is filtered off and receive 3-amino-4-morpholino-benzoic acid methyl ester, mp 189-191 ° C.
Смесь 82 г метилового эфира З-амино-4-морфолинобензойной кислоты, 500 мл этанола, 60 мл 10 н. водного раствора гидроокиси натри и 200 мл воды нагревают 3 час на паровой бане, обрабатывают 1 г активированного угл , фильтруют в гор чем состо нии, охлаждают фильтрат, подкисл ют его концентрированной сол ной кислотой до рП 3-4, отдел ют осадок и получают З-амиио-4-морфолинобензойную кислоту, т. ил. 250-252°С (разл.).A mixture of 82 g of methyl ester of 3-amino-4-morpholinobenzoic acid, 500 ml of ethanol, 60 ml of 10 n. an aqueous solution of sodium hydroxide and 200 ml of water is heated for 3 hours on a steam bath, treated with 1 g of activated carbon, filtered in a hot state, the filtrate is cooled, acidified with concentrated hydrochloric acid to pH 3-4, the precipitate is separated and obtained -amio-4-morpholinobenzoic acid, t. Il. 250-252 ° C (decomp.).
К смеси ПО г З-амино-4-морфолинобеизойной кислоты и 700 мл концентрированной сол ной кислоты при 0°С и перемешивании прикапывают раствор 50 г нитрита натри в 200 мл воды. Полученный раствор прибавл ют медленно при 10-15°С и перемещивании к раствору 80 г свежеприготовленного хлорида меди (I) в 300 мл концентрированной сол ной кислоты, перемешивают 1 час при комнатной температуре и разбавл ют водой. Отфильтрованный осадок раствор ют в водном растворе бикарбоната натри , обрабатывают активированным углем, фильтруют, подкисл ют фильтрат сол ной кислотой до рН 3-4, перекристаллизовывают осадок из и получают З-хлор-4-морфолинобензойную кислоту, т. пл. 195-1.96°С.A solution of 50 g of sodium nitrite in 200 ml of water is added dropwise to a mixture of PO g of 3-amino-4-morpholinobeisoic acid and 700 ml of concentrated hydrochloric acid at 0 ° C and stirring. The resulting solution was added slowly at 10-15 ° C and transferred to a solution of 80 g of freshly prepared copper (I) chloride in 300 ml of concentrated hydrochloric acid, stirred for 1 hour at room temperature and diluted with water. The filtered precipitate is dissolved in an aqueous solution of sodium bicarbonate, treated with activated carbon, filtered, the filtrate is acidified with hydrochloric acid to pH 3-4, the precipitate is recrystallized and 3-chloro-4-morpholino benzoic acid is obtained, m.p. 195-1.96 ° C.
38 г З-хлор-4-морфолинобензойной кислоты, 250 мл этанола и 17 мл концентрированной серной кислоты кип т т 1 час с обратным холодильником, выпаривают в вакууме, обрабатывают остаток льдом и насыщенным водным раствором карбоната кали до щелочной реакции, экстрагируют серным эфиром, сушат и выпаривают органический экстракт. Остаток перекристаллизовывают из смеси серный38 g of H-chloro-4-morpholinobenzoic acid, 250 ml of ethanol and 17 ml of concentrated sulfuric acid are boiled for 1 hour under reflux, evaporated in vacuo, the residue is treated with ice and a saturated aqueous solution of potassium carbonate until basic, extracted with sulfuric ether, dried and evaporated the organic extract. The residue is recrystallized from a mixture of sulfur
эфир-петролейный эфир и получают этиловый эфир З-хлор-4-морфолинобензойной кислоты , т. пл. 75-76°С.ether-petroleum ether and get ethyl ester Z-chloro-4-morpholinobenzoic acid, so pl. 75-76 ° C.
Раствор 30 г этилового эфира З-хлор-4-морфолинобензойной кислоты в 50 мл диоксанаA solution of 30 g of ethyl ester of 3-chloro-4-morpholinobenzoic acid in 50 ml of dioxane
прибавл ют по капл м при перемешивании к суспензии 5 г алюмогидрида лити в 400 мл диоксана, нагретой до 70°С, перемешивают 30 мин, охлаждают, разбавл ют осторожно водой и фильтруют. Остаток на фильтре промывают диоксаном, выпаривают фильтрат в вакууме, раствор ют остаток в серном эфире, взбалтывают раствор с активированным углем , фильтруют, выпаривают фильтрат, перекристаллизовывают остаток из смеси серныйwhile stirring, 5 g of lithium aluminum hydride in 400 ml of dioxane heated to 70 ° C are added dropwise with stirring, stirred for 30 minutes, cooled, diluted with water and filtered. The residue on the filter is washed with dioxane, the filtrate is evaporated in a vacuum, the residue is dissolved in sulfuric ether, the solution is stirred with activated carbon, filtered, the filtrate is evaporated, the residue is recrystallized from a mixture of sulfuric
эфир-петролейный эфир и выдел ют 3-хлор4-морфолинобензиловый спирт, т. пл. 80- .petroleum ether and isolate 3-chloro-4-morpholinobenzyl alcohol, m.p. 80-.
Смесь 17 г З-хлор-4-морфолинобензилового спирта, 200 мл бензола и 20 г тионилхлоридаA mixture of 17 g of 3-chloro-4-morpholinobenzyl alcohol, 200 ml of benzene and 20 g of thionyl chloride
кип т т 4 час с обратным холодильником, охлаждают , фильтруют, выпаривают фильтрат в вакууме, обрабатывают остаток лед ной водой и экстрагируют серным эфиром. Эфирный экстракт промывают водным раствором бикарбоната натри , фильтруют, выпаривают, перекристаллизовывают остаток из петролейного эфира и получают З-хлор-4-морфолинобензилхлорид , т. пл. 58-60°С.boil for 4 hours under reflux, cool, filter, evaporate the filtrate in vacuo, treat the residue with ice water and extract with sulfuric ether. The ether extract is washed with an aqueous solution of sodium bicarbonate, filtered, evaporated, the residue is recrystallized from petroleum ether and 3-chloro-4-morpholinobenzyl chloride is obtained, m.p. 58-60 ° C.
При1мер 2. З-Хлор-4-пиперидинофенилацетонитрил , т. пл. 55-56°С, получают, как в примере 1, из З-хлор-4-пиперидинобензилхлорида , который можно получить аналогично примеру 1 из З-нитро-4-пиперидинобензойнойWhen 1, 2. C-Chloro-4-piperidinophenylacetonitrile, so pl. 55-56 ° C, obtained as in example 1, from 3-chloro-4-piperidinobenzyl chloride, which can be obtained analogously to example 1 from 3-nitro-4-piperidinobenzoic
кислоты, т. пл. 198-201°С; З-амино-4-пиперидинобензойной кислоты, т. пл. 180°С; 3-хлор4-пиперидинобензойной кислоты, т. пл. 165- 167°С; этилового эфира З-хлор-4-пиперидипобензойной кислоты, т. пл. 48-49 С и т. кип.acids, so pl. 198-201 ° C; Z-amino-4-piperidinobenzoic acid, so pl. 180 ° C; 3-chloro-4-piperidinobenzoic acid, so pl. 165-167 ° C; ethyl ester of 3-chloro-4-piperidipobenzoic acid, so pl. 48-49 C and so on. Kip.
130°С/0,1 мм; З-хлор-4-пиперидинобензилового спирта, т. кип. 130°С/0,2 мм.130 ° C / 0.1 mm; H-chloro-4-piperidinobenzyl alcohol, t. Kip. 130 ° C / 0.2 mm.
Пример 3. Смесь 26,8 г N,N-димeтил-3хлор-4-пиперидинобензиламина , 15,6 г метилйодида и 200 мл безводного этанола кип т т 15 мин с -обратным холодильником, разбавл ют эфиром, образовавшеес четвертичное соединение отфильтровывают, раствор ют в небольшом количестве 50%-ного водного этанола , прибавл ют 66,4 г цианида кали и нагревают 8 час до 160°С в закрытом сосуде. После охлаждени экстрагируют эфиром, высушенный экстракт фильтруют, выпаривают и получают З-хлор-4-пиперидинофенилацетонитрил , т. пл. 55-56°С.Example 3. A mixture of 26.8 g of N, N-dimethyl-3chloro-4-piperidinobenzylamine, 15.6 g of methyl iodide and 200 ml of anhydrous ethanol was boiled for 15 minutes with a f-reverse, diluted with ether, the resulting quaternary compound was filtered, the solution in a small amount of 50% aqueous ethanol, 66.4 g of potassium cyanide are added and heated to 160 ° C for 8 hours in a closed vessel. After cooling, it is extracted with ether, the dried extract is filtered, evaporated and 3-chloro-4-piperidinophenylacetonitrile is obtained, m.p. 55-56 ° C.
Аналогично получают:Similarly, receive:
З-Хлоро-4-пирролидинофенилуксусную кислоту , т. пл. гидрохлорида 194-196 С (метанол-серный эфир);H-Chloro-4-pyrrolidinophenylacetic acid, m.p. hydrochloride 194-196 C (methanol-sulfur ether);
4-Пирролидинофенилуксусную кислоту, т. пл. 138-141°С;4-Pyrrolidinophenylacetic acid, so pl. 138-141 ° C;
а-Циклопропил - а - {4-пиперидинофенил)уксусную кислоту, т. пл. 149-15ГС (метанол );a-Cyclopropyl - a - {4-piperidinophenyl) acetic acid, so pl. 149-15GS (methanol);
4-Пиперидинофенилацетонитрил, т. пл. 64- (гексан);4-Piperidinophenylacetonitrile, so pl. 64- (hexane);
4-(3-Пирролип-1-ил)-фенилуксусную кислоту , т. пл. 162-165°С (этанол);4- (3-Pyrrolip-1-yl) -phenylacetic acid, so pl. 162-165 ° C (ethanol);
4-Морфолинофенилуксусную кислоту, т. пл. 111 - (этанол-серный эфир);4-morpholino-phenylacetic acid, m.p. 111 - (ethanol-sulfur ether);
а- (4-Пиперидинофенил) -пропионовую кислоту , т. пл. гидрохлорида 211-214°С (изопропанол-серный эфир);a- (4-Piperidinophenyl) -propionic acid, so pl. hydrochloride 211-214 ° C (isopropanol-sulfur ether);
Морфолинофенилуксусную кислоту, т. пл. 111 - 113°С (этанол-серный эфир);Morpholinophenylacetic acid, so pl. 111 - 113 ° C (ethanol-sulfur ether);
3-Пиперидинофенилуксусную кислоту, т. пл. гидрохлорида 242-245°С (вода);3-Piperidinophenylacetic acid, so pl. hydrochloride 242-245 ° C (water);
а- (4-Пирролидинофенил) -пропионовую кислоту , т. пл. 142°С (серный эфир-петролейный эфир);a- (4-Pyrrolidinophenyl) -propionic acid, so pl. 142 ° C (sulfuric ether-petroleum ether);
4-Ы-Гексаметиленаминофенилуксусную кислоту , т. пл. 100-102°С (серный эфир-петролейный эфир), т. пл. гидрохлорида 148- 15ГС;4-Y-Hexamethylaminophenylacetic acid, so pl. 100-102 ° C (sulfuric ether-petroleum ether), so pl. hydrochloride 148-15GS;
а-(3-Хлор-4-пиперидинофенил) - пропиоповую кислоту, т. пл. 95-97°С, (гексан), т. пл. натриевой соли 206-210С (серный эфир), т. лл. гидрохлорида 198-200°С (этанол-серный эфир);a- (3-Chloro-4-piperidinophenyl) - propiopic acid, so pl. 95-97 ° C, (hexane), m.p. sodium salt 206-210С (sulfuric ether), so l. hydrochloride 198-200 ° C (ethanol-sulfur ether);
4- (4-Метилпиперазнно) -фенилуксусную кислоту , т. пл. дигидрохлорида 220-223°С (изопропанол );4- (4-Methylpiperazno) -phenylacetic acid, so pl. dihydrochloride 220-223 ° C (isopropanol);
а-(3-Нитро-4-пиперидинофенил) - пропионовую кислоту, т. пл. 206-208°С (этанол-серный эфир);a- (3-Nitro-4-piperidinophenyl) - propionic acid, so pl. 206-208 ° C (ethanol-sulfur ether);
а-(4-М-Гексаметиленаминофенил) - пропионовую кислоту, т. пл. гидрохлорида 196- 199°С (этанол);a- (4-M-Hexamethylene-aminophenyl) - propionic acid, t. pl. hydrochloride salt 196- 199 ° C (ethanol);
сх-(3-Хлор-4-пилеридинофенил) - а - циклопропилуксусную кислоту, т. пл. 129-13 ГС (циклогексан и н-гексан-циклогексап);CX- (3-Chloro-4-pilyridinophenyl) - a - cyclopropylacetic acid, so pl. 129-13 GS (cyclohexane and n-hexane-cyclohexap);
а-(3-Амино-4-пиперидинофенил) - пропионовую кислоту, т. пл. 148-15ГС (этилацетат );a- (3-Amino-4-piperidinophenyl) - propionic acid, so pl. 148-15GS (ethyl acetate);
4- (4-Оксипиперидинофенил) -уксусную кислоту , т. пл. натриевой соли 261-264°С (этанол );4- (4-hydroxypiperidinophenyl) acetic acid, so pl. sodium salt 261-264 ° C (ethanol);
(4-Оксипиперидино)-фенил - пропионовую кислоту, т. пл. натриевой соли 270- 274°С (изопропанол);(4-hydroxypiperidino) -phenyl - propionic acid, so pl. sodium salt 270-274 ° C (isopropanol);
(3-Пирролин-1-ил)-фенил - циклопропилпропионовую кислоту, т. пл. 135-137°С (серный эфир).(3-Pyrrolin-1-yl) -phenyl - cyclopropylpropionic acid, so pl. 135-137 ° C (sulfuric ether).
Пример 4. Раствор 8 г З-хлор-4-морфолннофенилацетонитрила в 100 мл этанола обрабатывают 4 г гидроокиси кали в 40 мл воды и кип т т 16 час с обратным холодильником. Выпаривают смесь в вакууме, обрабатывают остаток 150 мл воды, прибавл ют 0,5 г актит-:Ированпого угл и фильтруют. Подкисл ютExample 4. A solution of 8 g of 3-chloro-4-morpholophenylacetonitrile in 100 ml of ethanol is treated with 4 g of potassium hydroxide in 40 ml of water and boiled for 16 hours under reflux. The mixture is evaporated in vacuo, the residue is taken up in 150 ml of water, 0.5 g of aktivite is added: Irovanpogo coal and filtered. Acidified
66
фильтрат 2 п. сол ной кислотой до , экстрагируют серным эфиром, промывают экстракт водой, сушат, выпаривают и перекристаллизовывают остаток из смеси серный эфир - петролейный эфир. Получают 3-хлор4-морфолинофенилуксусную кислоту, т. пл. 125-126°С.the filtrate 2 p. hydrochloric acid before, extracted with sulfuric ether, the extract is washed with water, dried, evaporated and the residue is recrystallized from a mixture of sulfuric ether - petroleum ether. Get 3-chloro-4-morpholinophenylacetic acid, so pl. 125-126 ° C.
Пример 5. Раствор 2 г З-хлор-4-пиперидинофенилап ,етопитрила в 150 мл этиленгликол обрабатывают 5 г гидроокиси кали в 30 мл воды, нагревают 18 час при 130-140°С, охлаждают, разбавл ют 400 мл воды, подкисл ют 2 и. сол ной кислотой до рП 3 и экстрагируют серным эфиром. Взбалтывают экстракт с насыщенным водным раствором бикарбоната натри , водную фазу подкисл ют 2 н. сол ной кислотой до и экстрагируют серным эфиром. Высушенный экстракт выпаривают, перекристаллизовывают остатокExample 5. A solution of 2 g of 3-chloro-4-piperidinophenyl, ethopitrile in 150 ml of ethylene glycol is treated with 5 g of potassium hydroxide in 30 ml of water, heated for 18 hours at 130-140 ° C, cooled, diluted with 400 ml of water, acidified 2 and. hydrochloric acid to rp 3 and extracted with sulfuric ether. The extract is shaken with a saturated aqueous solution of sodium bicarbonate, the aqueous phase is acidified with 2N. hydrochloric acid before and extracted with sulfuric ether. The dried extract is evaporated, the residue is recrystallized
из смеси серный эфир-петролейный эфир и выдел ют З-хлор-4-пиперидипофенилуксусную кислоту, т. пл. 106-107°С.from a mixture of sulfuric ether-petroleum ether and isolate 3-chloro-4-piperidipophenylacetic acid, m.p. 106-107 ° C.
Пример 3. с .моши.вают этанольные насышенные растворы 2 г -а-(3-хлор-4-пиперидинофенил )-пронионовой кислоты и 1,18 г /-а-(1нафтил )-этиламина в этаноле, отфильтровывают осадок и перекристаллизовывают его несколько раз из этанола, т. пл. соли 140- 142°С. 0,27 г этой соли раствор ют в 15 млExample 3. ethanol soluted ethanol solutions of 2 g of a- (3-chloro-4-piperidinophenyl) -pronionic acid and 1.18 g of a-a- (1-naphthyl) ethylamine in ethanol, the precipitate is filtered and recrystallized several times from ethanol, t. pl. salts 140-142 ° C. 0.27 g of this salt is dissolved in 15 ml
6 н. водного расгвора гидроокиси натри , промывают сорным эФ::ром, подкисл ют 6 н. сол ной кислотой .И) pli 5,5. и экстрагируют серным эфиром. Промытый водой экстракт сушат, фильтруют, выпаривают и получают6 n. sodium hydroxide solution, washed with trash EF :: rum, acidified with 6N. hydrochloric acid .and) pli 5.5. and extracted with sulfuric ether. Washed with water, the extract is dried, filtered, evaporated and get
/-а-(3-хлор-4 - пипери„инофснил) - проппоновую кислоту, -38° (этанол).I-a- (3-chloro-4-piperi inofsnil) - propponic acid, -38 ° (ethanol).
Смешивают насышенные растворы 3,67 г dlа- (3-хлор-4-пиперидинофенил) - пропионовойMix rich solutions of 3.67 g of dl- (3-chloro-4-piperidinophenyl) - propionic
кислоты и 2,3 г й-ос-(1-нафтил)-этиламина в этаноле, отфильтровывают осадок, перекристаллизовывают его несколько раз из этанола и получают соль, т. пл. 141 - 142С, 0,34 г которой раствор ют в 20 мл 6 н. водного раствора гидроокиси натри , промывают раствор серным эфиром, подкисл ют 6 н. сол ной кислотой до рН 5,5 и экстрагируют серным эфиром . Органический экстракт промывают водой , cyniaT, фильтруют, выпаривают и получают й-а-(3-хлор-4-пиперидинофенпл)-припионовую кислоту, +39, (этанол).acids and 2.3 g of C-o- (1-naphthyl) ethylamine in ethanol, the precipitate is filtered off, it is recrystallized several times from ethanol, and salt is obtained, mp. 141 - 142 ° C, 0.34 g of which is dissolved in 20 ml of 6 N an aqueous solution of sodium hydroxide, washed with sulfuric ether, acidified with 6N. hydrochloric acid to pH 5.5 and extracted with sulfuric ether. The organic extract is washed with water, cyniaT, filtered, evaporated, and y-a- (3-chloro-4-piperidinophenpl) -pyridionic acid, +39, (ethanol) is obtained.
Пример 7. При обработке концентрированного раствора 2,33 г а-(4-пИПеридинофенил )-пропионовой кислоты в серном эфире 0,45 г этиламина нолучают соответствующую аминную соль, т. пл. 167-170 С (этанол- серный эфир).Example 7. When treating a concentrated solution of 2.33 g of a- (4-piperidinophenyl) propionic acid in sulfuric ester of 0.45 g of ethylamine, the corresponding amine salt is obtained, so pl. 167-170 C (ethanol-sulfur ether).
Аналогично получают соли а-(4пиперидинофенил )-пропгюновой кислоты при обработке этаиоламипом (0,61 г),Similarly, salts of a- (4piperidinophenyl) -propyunic acid are obtained by treatment with ethanolamine (0.61 g),
т. пл. 109-Г|2 С (этапе,-:-серный эфир); 2диметиламш-юэтаполом (0,89 г),m.p. 109-G | 2 C (stage, -: - sulfur ether); 2dimethylamsh-yuetapol (0.89 g),
т. пл. 73-75С (этанол-серный эфир); нгексилам1П10м (1,01 г). т. пл. 136-138°С (этилацетат); пирролидином (0,71 г), т. пл. 127-129°С (этилацетат); пиперидином (0,85 г), т. пл. 143-145°С (этилацетат), и морфолином (0,87 г), т. пл. 117- 120°С (этилацетат). Предмет изобретени Способ получени третичных аминокислот общей формулы O-Ph-C-coOH R где Ri - водород, низший алкил; R2 - водород , алкил, циклоалкил, циклоалкил-низший алкил; Ph - замещенный или незамещенный фенилен; А - незамещенный или замещенный на ОКСО-, окси- или алканоилоксигрунпу низший алкилен, низщнй алкенилен, низщий азаалкилен , ннзщий оксаалкилен или низший тиаалкилен , причем два гетероатома отделены друг от друга по меньшей мере одним атомом углерода, или их солей, отличающийс тем, что соединение общей формулы -чRI А N-Ph-c-R -1 5 где RI, R2, Ph и А имеют выщеуказанные значени ; Rs - реакционноспособна этерифицированна в простой или сложный эфир оксигруппа , например, галоид или алммониева группа, подвергают взаимодействию с цианидом щелочного металла, полученный нитрил кислоты гидролизуют с последующим выделением целевого продукта в виде основани или переведением его в соль известным способом. Приоритет по признакам: 27.03.68 при RI - водород, низший алкил; R2 - водород, алкил, Сз-Су-циклоалкил; Ph - замещенный или незамещенный фенилен; А - низщий алкнлен, низщий моноазаалкилен , низщий монооксаалкилен, низщий монотнаалкилен; два имеющихс гетероатома отделены друг от друга двум атомами углерода; Rs - реакцнонноспособна этерифнцированна в простой эфир окснгруппа, нанример, галоид; 03.09.68при R2 - циклоалкил или циклоалкил-низший алкил; А - низший алкилен, низший азаалкилен, низший оксаалкилен, низший тиаалкилен; Ra - реакционноснособна этерифнцированна в простой эфир оксигруппа, аммониева грунпа; 13.01.69при А - низший алкилен или низший алкенилен, замещенные на оксо-, оксиили низщую алканоилоксигруппу; два имеющихс гетероатома отделены друг от друга по меньшей мере одним атомом углерода.m.p. 73-75C (ethanol-sulfur ether); nhexyl amide1P10m (1.01 g). m.p. 136-138 ° C (ethyl acetate); pyrrolidine (0.71 g), so pl. 127-129 ° C (ethyl acetate); piperidine (0.85 g), so pl. 143-145 ° C (ethyl acetate), and morpholine (0.87 g), so pl. 117-120 ° C (ethyl acetate). The subject of the invention. A method for producing tertiary amino acids of the general formula: O-Ph-C-coOH R where Ri is hydrogen, lower alkyl; R2 is hydrogen, alkyl, cycloalkyl, cycloalkyl-lower alkyl; Ph is substituted or unsubstituted phenylene; A - unsubstituted or substituted lower alkylene, lower alkenylene, lower azaalkylene, lower oxaylene or lower thiaalkylene, which has two heteroatoms separated from each other by at least one carbon atom, or their salts, which are different from OXO-, hydroxy- or alkanoyloxygrume; The compound of the general formula is -RI. N-Ph-cR -1 5 where RI, R2, Ph and A are as defined above; Rs is a hydroxy esterified reactive esterified into ester or ester, for example, a halide or an ammonium group, is reacted with an alkali metal cyanide, the resulting acid nitrile is hydrolyzed, followed by isolation of the desired product in the salt by a known method. Priority signs: 03/27/68 when RI is hydrogen, lower alkyl; R2 is hydrogen, alkyl, C3-Su-cycloalkyl; Ph is substituted or unsubstituted phenylene; A - lower alkylene, lower monoazalkylene, lower monooxalkylene, lower monotnaalkylene; two available heteroatoms are separated from each other by two carbon atoms; Rs is a reactive esterifing to a simple ether, oxngroup, nanorimer, halide; 09/03/68 when R2 is cycloalkyl or cycloalkyl-lower alkyl; A - lower alkylene, lower azaalkylene, lower oxaalkylene, lower thiaalkylene; Ra is a reactive esterifed to ether ether, ammonium subsoil; 01.13.69-A-lower alkylene or lower alkenylene, substituted by oxo-, oxyl or lower alkanoyloxy group; the two available heteroatoms are separated from each other by at least one carbon atom.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US71634768A | 1968-03-27 | 1968-03-27 | |
US75713668A | 1968-09-03 | 1968-09-03 | |
US79086369A | 1969-01-13 | 1969-01-13 |
Publications (1)
Publication Number | Publication Date |
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SU419029A3 true SU419029A3 (en) | 1974-03-05 |
Family
ID=27418953
Family Applications (4)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
SU1493629A SU421191A3 (en) | 1968-03-27 | 1969-03-25 | METHOD FOR OBTAINING TERTIARY ALTIINO ACIDES OR THEIR COMPLEX ETHERS, OR AMIDES, OR SALTS THEREOF |
SU1815022A SU459886A3 (en) | 1968-03-27 | 1969-03-25 | The method of obtaining - (aminophenyl) aliphatic carboxylic acids or their salts |
SU1493628A SU419029A3 (en) | 1968-03-27 | 1969-03-25 | METHOD FOR OBTAINING TERTIARY AMINO ACIDS OF THEIR SALTS |
SU1493626A SU428600A3 (en) | 1968-03-27 | 1969-03-25 | METHOD OF OBTAINING TERTIARY AMINO ACIDS OR THEIR SALTS |
Family Applications Before (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
SU1493629A SU421191A3 (en) | 1968-03-27 | 1969-03-25 | METHOD FOR OBTAINING TERTIARY ALTIINO ACIDES OR THEIR COMPLEX ETHERS, OR AMIDES, OR SALTS THEREOF |
SU1815022A SU459886A3 (en) | 1968-03-27 | 1969-03-25 | The method of obtaining - (aminophenyl) aliphatic carboxylic acids or their salts |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
SU1493626A SU428600A3 (en) | 1968-03-27 | 1969-03-25 | METHOD OF OBTAINING TERTIARY AMINO ACIDS OR THEIR SALTS |
Country Status (26)
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JP (1) | JPS5330712B1 (en) |
AR (7) | AR192699A1 (en) |
AT (8) | AT291237B (en) |
BE (1) | BE730520A (en) |
BG (3) | BG20339A3 (en) |
CH (11) | CH563989A5 (en) |
CS (8) | CS153503B2 (en) |
CY (1) | CY809A (en) |
DE (1) | DE1913743A1 (en) |
DK (1) | DK145226C (en) |
FI (1) | FI52579C (en) |
FR (1) | FR2004827A1 (en) |
GB (1) | GB1268831A (en) |
IE (1) | IE33153B1 (en) |
IL (1) | IL31861A (en) |
KE (1) | KE2542A (en) |
MY (1) | MY7500152A (en) |
NL (1) | NL162647C (en) |
NO (1) | NO132199C (en) |
OA (1) | OA03609A (en) |
PH (1) | PH12640A (en) |
PL (1) | PL74820B1 (en) |
RO (4) | RO66273A (en) |
SE (1) | SE382812B (en) |
SU (4) | SU421191A3 (en) |
YU (3) | YU39926B (en) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE2025518A1 (en) * | 1969-06-05 | 1970-12-10 | ||
DE2013376A1 (en) * | 1970-03-20 | 1971-10-07 | Merck Patent Gmbh | Substituted phenylacetic acids and processes for their preparation |
-
1969
- 1969-02-17 CH CH1447371A patent/CH563989A5/xx not_active IP Right Cessation
- 1969-02-17 CH CH1446771A patent/CH563984A5/xx not_active IP Right Cessation
- 1969-02-17 CH CH1446871A patent/CH554859A/en not_active IP Right Cessation
- 1969-02-17 CH CH1396773A patent/CH559755A5/xx not_active IP Right Cessation
- 1969-02-17 CH CH1371573A patent/CH563985A5/xx not_active IP Right Cessation
- 1969-02-17 CH CH1447071A patent/CH563986A5/xx not_active IP Right Cessation
- 1969-02-17 CH CH1446671A patent/CH563983A5/xx not_active IP Right Cessation
- 1969-02-17 CH CH1447271A patent/CH563988A5/xx not_active IP Right Cessation
- 1969-03-03 NL NL6903273.A patent/NL162647C/en not_active IP Right Cessation
- 1969-03-18 DE DE19691913743 patent/DE1913743A1/en active Pending
- 1969-03-20 IL IL31861A patent/IL31861A/en unknown
- 1969-03-24 SE SE6904047A patent/SE382812B/en unknown
- 1969-03-25 IE IE397/69A patent/IE33153B1/en unknown
- 1969-03-25 SU SU1493629A patent/SU421191A3/en active
- 1969-03-25 SU SU1815022A patent/SU459886A3/en active
- 1969-03-25 PL PL13255169A patent/PL74820B1/pl unknown
- 1969-03-25 SU SU1493628A patent/SU419029A3/en active
- 1969-03-25 SU SU1493626A patent/SU428600A3/en active
- 1969-03-25 FR FR6908705A patent/FR2004827A1/fr active Pending
- 1969-03-26 AT AT281570A patent/AT291237B/en not_active IP Right Cessation
- 1969-03-26 GB GB05859/69A patent/GB1268831A/en not_active Expired
- 1969-03-26 AT AT282070A patent/AT291242B/en not_active IP Right Cessation
- 1969-03-26 AT AT281970A patent/AT291241B/en not_active IP Right Cessation
- 1969-03-26 DK DK167569A patent/DK145226C/en not_active IP Right Cessation
- 1969-03-26 AT AT281870A patent/AT291240B/en not_active IP Right Cessation
- 1969-03-26 AT AT281370A patent/AT291235B/en not_active IP Right Cessation
- 1969-03-26 AT AT281770A patent/AT291239B/en not_active IP Right Cessation
- 1969-03-26 FI FI690885A patent/FI52579C/en active
- 1969-03-26 AT AT298169A patent/AT287685B/en active
- 1969-03-26 BE BE730520A patent/BE730520A/xx not_active IP Right Cessation
- 1969-03-26 CY CY809A patent/CY809A/en unknown
- 1969-03-26 NO NO1264/69A patent/NO132199C/no unknown
- 1969-03-26 AT AT281270A patent/AT291234B/en not_active IP Right Cessation
- 1969-03-27 CS CS725570A patent/CS153503B2/cs unknown
- 1969-03-27 CS CS725870A patent/CS153506B2/cs unknown
- 1969-03-27 BG BG019310A patent/BG20339A3/en unknown
- 1969-03-27 CS CS220869A patent/CS153502B2/cs unknown
- 1969-03-27 CS CS726270A patent/CS153510B2/cs unknown
- 1969-03-27 RO RO6979091A patent/RO66273A/en unknown
- 1969-03-27 CS CS726070A patent/CS153508B2/cs unknown
- 1969-03-27 CS CS726370A patent/CS153511B2/cs unknown
- 1969-03-27 RO RO6978690A patent/RO66269A/en unknown
- 1969-03-27 OA OA53565A patent/OA03609A/en unknown
- 1969-03-27 BG BG019345A patent/BG20567A3/en unknown
- 1969-03-27 CS CS725770A patent/CS153505B2/cs unknown
- 1969-03-27 RO RO6978689A patent/RO64901A/en unknown
- 1969-03-27 BG BG019132A patent/BG20340A3/en unknown
- 1969-03-27 CS CS725670A patent/CS153504B2/cs unknown
- 1969-03-27 RO RO59517A patent/RO61382A/ro unknown
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1970
- 1970-08-03 AR AR230415A patent/AR192699A1/en active
- 1970-08-03 AR AR230413A patent/AR193024A1/en active
- 1970-08-03 AR AR230419A patent/AR192864A1/en active
- 1970-08-03 AR AR230412A patent/AR193194A1/en active
- 1970-08-03 AR AR230414A patent/AR192560A1/en active
- 1970-08-03 AR AR230420A patent/AR193025A1/en active
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1971
- 1971-05-13 AR AR235528A patent/AR194569A1/en active
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1972
- 1972-03-23 JP JP2863972A patent/JPS5330712B1/ja active Pending
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1973
- 1973-09-07 PH PH15001A patent/PH12640A/en unknown
-
1974
- 1974-07-17 YU YU2001/74A patent/YU39926B/en unknown
- 1974-07-17 YU YU2000/74A patent/YU39653B/en unknown
- 1974-08-22 CH CH238069A patent/CH566990A5/xx not_active IP Right Cessation
- 1974-11-01 CH CH238069A patent/CH563381A5/xx not_active IP Right Cessation
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1975
- 1975-02-21 CH CH238069A patent/CH566991A5/xx not_active IP Right Cessation
- 1975-06-10 YU YU1499/75A patent/YU39532B/en unknown
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- 1975-12-30 MY MY152/75A patent/MY7500152A/en unknown
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