DE2551728A1 - PROCESS FOR PRODUCTION OF ALPHA-AMINO-1-ADAMANTYLACETIC ACID - Google Patents
PROCESS FOR PRODUCTION OF ALPHA-AMINO-1-ADAMANTYLACETIC ACIDInfo
- Publication number
- DE2551728A1 DE2551728A1 DE19752551728 DE2551728A DE2551728A1 DE 2551728 A1 DE2551728 A1 DE 2551728A1 DE 19752551728 DE19752551728 DE 19752551728 DE 2551728 A DE2551728 A DE 2551728A DE 2551728 A1 DE2551728 A1 DE 2551728A1
- Authority
- DE
- Germany
- Prior art keywords
- acid
- amino
- solution
- ester
- adamantylmalonic
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- NJRFVURYVWPLKB-UHFFFAOYSA-N 2-(1-adamantyl)-2-aminoacetic acid Chemical compound C1C(C2)CC3CC2CC1(C(C(O)=O)N)C3 NJRFVURYVWPLKB-UHFFFAOYSA-N 0.000 title claims abstract description 15
- 238000000034 method Methods 0.000 title claims abstract description 12
- 238000004519 manufacturing process Methods 0.000 title description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims abstract description 12
- GWJUQQKLUYCIIH-UHFFFAOYSA-N diethyl 2-(1-adamantyl)propanedioate Chemical compound C1C(C2)CC3CC2CC1(C(C(=O)OCC)C(=O)OCC)C3 GWJUQQKLUYCIIH-UHFFFAOYSA-N 0.000 claims abstract description 8
- LGWCCPHMJDZDHZ-UHFFFAOYSA-N 2-(1-adamantyl)-3-ethoxy-3-oxopropanoic acid Chemical compound C1C(C2)CC3CC2CC1(C(C(O)=O)C(=O)OCC)C3 LGWCCPHMJDZDHZ-UHFFFAOYSA-N 0.000 claims abstract description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims abstract description 7
- RXPUCZKBHCQYMB-UHFFFAOYSA-N CCOC(C(C1(CC(C2)C3)CC3CC2C1)C(O)=O)=O.Cl Chemical compound CCOC(C(C1(CC(C2)C3)CC3CC2C1)C(O)=O)=O.Cl RXPUCZKBHCQYMB-UHFFFAOYSA-N 0.000 claims abstract description 5
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 claims abstract description 5
- 239000005708 Sodium hypochlorite Substances 0.000 claims abstract description 4
- 230000007062 hydrolysis Effects 0.000 claims abstract description 4
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract description 4
- 238000002360 preparation method Methods 0.000 claims abstract description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 20
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 18
- 239000000243 solution Substances 0.000 claims description 17
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 12
- 239000002244 precipitate Substances 0.000 claims description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Natural products CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
- 230000001476 alcoholic effect Effects 0.000 claims description 5
- 239000000706 filtrate Substances 0.000 claims description 5
- 238000003756 stirring Methods 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 3
- 238000009835 boiling Methods 0.000 claims description 3
- 230000015556 catabolic process Effects 0.000 claims description 3
- 238000001816 cooling Methods 0.000 claims description 3
- 238000006731 degradation reaction Methods 0.000 claims description 3
- 150000002500 ions Chemical class 0.000 claims description 3
- 229920001467 poly(styrenesulfonates) Polymers 0.000 claims description 3
- 239000011541 reaction mixture Substances 0.000 claims description 3
- 239000007864 aqueous solution Substances 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims 2
- 230000009435 amidation Effects 0.000 claims 1
- 238000007112 amidation reaction Methods 0.000 claims 1
- 150000002168 ethanoic acid esters Chemical class 0.000 claims 1
- 238000001914 filtration Methods 0.000 claims 1
- 230000000977 initiatory effect Effects 0.000 claims 1
- 238000007127 saponification reaction Methods 0.000 claims 1
- 229910021529 ammonia Inorganic materials 0.000 abstract 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 abstract 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 2
- DACIGVIOAFXPHW-UHFFFAOYSA-N 1-(1-adamantyl)ethanone Chemical compound C1C(C2)CC3CC2CC1(C(=O)C)C3 DACIGVIOAFXPHW-UHFFFAOYSA-N 0.000 description 1
- VQYXDIHZFDPTTL-UHFFFAOYSA-N 2-(1-adamantyl)-2-oxoacetic acid Chemical compound C1C(C2)CC3CC2CC1(C(=O)C(=O)O)C3 VQYXDIHZFDPTTL-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- 229910019093 NaOCl Inorganic materials 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- 108010087702 Penicillinase Proteins 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- DZULQZKFBAHSRX-UHFFFAOYSA-N adamantane-1-carbaldehyde Chemical compound C1C(C2)CC3CC2CC1(C=O)C3 DZULQZKFBAHSRX-UHFFFAOYSA-N 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 239000003637 basic solution Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- NYDGUAAQLKCFQD-UHFFFAOYSA-N ethyl 2-(1-adamantyl)acetate Chemical compound C1C(C2)CC3CC2CC1(CC(=O)OCC)C3 NYDGUAAQLKCFQD-UHFFFAOYSA-N 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229950009506 penicillinase Drugs 0.000 description 1
- 150000002960 penicillins Chemical class 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/56—Ring systems containing bridged rings
- C07C2603/58—Ring systems containing bridged rings containing three rings
- C07C2603/70—Ring systems containing bridged rings containing three rings containing only six-membered rings
- C07C2603/74—Adamantanes
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
Verfahren zur Herstellung von α-Amino-1-adamantylessigsäure. Process for the preparation of α-amino-1-adamantylacetic acid.
Die Erfindung betrifft das Verfahren zur Herstellung von α-Amino-1-adamantylessigsäure der Formel I Es ist bekannt, dass α-Amino-1-adamantylessigsäure (I) dadurch hergestellt werden kann, dass man gemEss der US-PS 3 325 478 vorgeht: a) 1-Adamantylcarboxaldehyd wird mit Ammoniumchlorid, Ammoniumhydroxid und Kaliumeyanid zu 1-Amino-1-(1-adamantyl)-acetonitril umgesetzt, das durch Hydrolyse in salssaurem Medium in a-Amino-1-adamantylessigsäure übergeht; b) 1-Acetyladamantan wird durch Oxydation mit Kaliumpermanganat in 1-Adamantylglyoxylsäure überführt, die mit Hydroxylamin 1-Adamantylglyoxyloxim ergibt, woraus man durch Reduktion mit Zink in Essigsäure α-Amino-1-adamantylessigsäure erhalt.The invention relates to the process for the preparation of α-amino-1-adamantylacetic acid of the formula I. It is known that α-amino-1-adamantyl acetic acid (I) can be prepared by proceeding according to US Pat. No. 3,325,478: a) 1-Adamantylcarboxaldehyde is converted into 1-amino-1 with ammonium chloride, ammonium hydroxide and potassium yanide - (1-adamantyl) acetonitrile reacted, which is converted into α-amino-1-adamantyl acetic acid by hydrolysis in a hydrochloric acid medium; b) 1-Acetyladamantane is converted into 1-adamantylglyoxylic acid by oxidation with potassium permanganate, which with hydroxylamine gives 1-adamantylglyoxyloxime, from which α-amino-1-adamantylacetic acid is obtained by reduction with zinc in acetic acid.
Es wurde nun gefungen, dass α-Amino-1-adamantylessigsäure (I) aus leicht zugänglichem 1-Adamantylmalonsäurediäthylester in guter Ausbeute gemGss folgender Reaktionsfolge einfach erhalten werden kann Das Verfahren ist dadurch gekennzeichnet, dass der durch patielle Hydrolyse von 1-Adamantylmalonsäurediäthylester (II) erhaltene 1-Adamantylmalonsäuremonoäthylester (III) mit Thionylchlorid in 1-Adamantylmalonsäuremonoäthylester-monochlorid (IV) übergeführt wird, der mit Ammoniakgas a-Carbonami.do-(V) 1-adamantylessigsäureäthylester ergibt, woraus durch Hofmann's Abbau α-Amino-1-adamantylessigsäure (I) erhalten wird.It has now been found that α-amino-1-adamantyl acetic acid (I) can be easily obtained from easily accessible 1-adamantylmalonic acid diethyl ester in good yield according to the following reaction sequence The process is characterized in that the 1-adamantylmalonic acid monoethyl ester (III) obtained by partial hydrolysis of 1-adamantylmalonic acid diethyl ester (II) is converted with thionyl chloride into 1-adamantylmalonic acid monoethyl ester monochloride (IV), which is converted with ammonia gas a-Carbonami.do- (V. ) 1-adamantylacetic acid ethyl ester results, from which α-amino-1-adamantylacetic acid (I) is obtained by Hofmann's degradation.
Nach dem erfindungsgemässen Verfahren wird eine alkoholische Lösung von 1-Adamantylmalonsäurediäthylester (II) mit einer alkoholischen Kaliumhydroxid-Lösung 7 Stunden bei 2rOC gerührt, dann wird Alkohol abdestilliert, der verbleibende Niederschlag des Kaliumsalzes von 1-Adamantylmalonsäureäthyl ester in Wasser gelöst und mit Ionenaustauscher DOWEX 50 (H+) vermischt, der ausgefallene Niederschlag mit Äther extrahiert und ether abdestilliert. Der erhaltene 1-Adamantylmalonsäuremonoäthylester (III) wird in trockenem Benzol gelöst, mit Thionylchlorid versetzt und die Reaktionslösung wird 4 Stunden bei 60°C gerührt, das Benzol wird abdestilliert, das ausgefallene 1-Adamantylmalonsäuremonoäthylestermonochlorid (IV) wird in trockenem Methylenchlorid gelöst und Ammoniakgas wird während 40 Minuten bei 0°C in die Lösung eingeführt. Der ausgefallene Niederschlag wird abfiltriert und das Filtrat wird durch Destillation vom Methylenchlorid befreit. Der erhaltene α-Carbonamido-1-adamantylessigsäureäthylester (V) wird in eine basische LUsung von Natriumhypochlorid gegeben und 1 Stunde bei Siedetemperatur (des Gemisches) stehengelassen.According to the inventive method, an alcoholic solution of 1-Adamantylmalonsäurediethylester (II) with an alcoholic potassium hydroxide solution Stirred for 7 hours at 2rOC, then alcohol is distilled off, the remaining precipitate the potassium salt of 1-Adamantylmalonsäureäthyl ester dissolved in water and with ion exchanger DOWEX 50 (H +) mixed, the precipitate extracted with ether and extracted ether distilled off. The 1-Adamantylmalonsäuremonoäthylester (III) obtained is dissolved in dry benzene, mixed with thionyl chloride and the reaction solution is stirred for 4 hours at 60 ° C, the benzene is distilled off, the precipitated 1-Adamantylmalonsäuremonoäthylestermonochlorid (IV) is in dry methylene chloride dissolved and ammonia gas is introduced into the solution at 0 ° C. for 40 minutes. The deposited precipitate is filtered off and the filtrate is distilled freed from methylene chloride. The obtained α-carbonamido-1-adamantyl acetic acid ethyl ester (V) is placed in a basic solution of sodium hypochlorite and treated for 1 hour Boiling temperature (of the mixture) left to stand.
Durch Ansäuren der Reaktionslösung wird α-Amino-1-adamantyl-(I) essigsäure isoliert.By acidifying the reaction solution, α-amino-1-adamantyl- (I) acetic acid isolated.
Die Verbindungen (III), (IV) und CV) sind bisher nicht beschrieben worden und werden gemäss vorliegender Erfindung im einzelnen nach bekannten Verfahren isoliert und charakterisiert.The compounds (III), (IV) and CV) have not yet been described and are according to the present invention in detail by known methods isolated and characterized.
Das durch dieses Verfahren erhaltene Endprodukt a-Amino-1-adamantylessigsäure (1) sowie Zwischenprodukte (III), (IV) und (V) sind als Ausgangsstoffe für organische Synthesen vielseitig verwendbar, während a-Amino-1 adamantylossigsäure an sich zur Herstellung von halbsynthetischen Penicillinen dient, die ein breites antibakterielles Wirkungsspektrum, eine Stabilität in saurem Medium sowie in Gegenwart von Penicillinase aufweisen (US-PS 3 325 478).The final product obtained by this process, α-amino-1-adamantylacetic acid (1) and intermediates (III), (IV) and (V) are used as starting materials for organic Syntheses can be used in many ways, while a-amino-1 adamantylossetic acid per se Manufacture of semi-synthetic penicillins is used, which is a broad antibacterial Spectrum of activity, stability in acidic medium and in the presence of penicillinase (U.S. Patent 3,325,478).
Die Erfindung wird durch folgende Beispiele illustriert: Beispiel 1 1-Adamantylmalonsäuremonoäthylester Zur Lösung von 5,714 g (0,0195 Mol) 1-Adamantylmalonsäurediäthylester in 23 ml absolutem Methanol werden unter Ruhren innerhalb elner Stunde bei 250C 39 ml (0,0392 Mol) 1 molare alkoholische Kaliumlauge zugetropft und noch 6 Stunden weitergerZhrt. Dann wird der Alkohol durch Destillation entfernt, der ausgefallene Niederschlag des Kaliumsalzes von 1-Adamantylmalonsäureäthylester abgesaugt, mit Ether gewaschen und dann in 35 ml Wasser gelöst. Die wässrige Lösung: wird mit 200 ml ether überschichtet und langsam durch heftiges Rühren mit 25 ml Ionenaustauscher DOWEX 50 (H+) versetzt, wobei 1-Adamantylmalonsäuremonoäthylester sich abtrennt und in. die Ätherschicht übergeht.The invention is illustrated by the following examples: Example 1 1-Adamantylmalonic acid monoethyl ester For a solution of 5.714 g (0.0195 mol) of 1-adamantylmalonic acid diethyl ester in 23 ml of absolute methanol are stirred within an hour at 250C 39 ml (0.0392 mol) of 1 molar alcoholic potassium hydroxide solution were added dropwise and a further 6 hours continued. Then the alcohol, the precipitated one, is removed by distillation The precipitate of the potassium salt of 1-Adamantylmalonsäureäthylester sucked off, with Washed ether and then dissolved in 35 ml of water. The aqueous solution: becomes with 200 ml of ether and slowly by vigorous stirring with 25 ml of ion exchanger DOWEX 50 (H +) added, 1-Adamantylmalonsäuremonoäthylester separates and passes into the ether layer.
Der Ether wird getrocknet und dann abdestilliert, wobei 4,2 g (82,5 %) 1-Adamantylmalonsäuremonoäthylester mit Schmp.The ether is dried and then distilled off, yielding 4.2 g (82.5 %) 1-Adamantylmalonsäuremonoäthylester with mp.
82-84°C ausgeschieden wird und aus Hexan umkristallisiert werden kann. Der Schmelzpunkt des umkristallisierten 1-Adamantylmalonsäuremonoäthylesters liegt bei 86-87°C.82-84 ° C is precipitated and can be recrystallized from hexane. The melting point of the recrystallized 1-Adamantylmalonsäuremonoäthylester is at 86-87 ° C.
Beispiel 2 1-Adamantylmalonsäuremonoäthylestermonochlorid Zur Lösung von 5 g (0,0188 Mol) 1-Adamantylmalonsäuremonoäthylester in 50 ml trockenem Benzol wird stufenweise 5 ml (0,069 Mol) Thionylchlorid zugetropft und die Reaktionslösung wird 90 minuten bei 600C erwärmt. Dann wird Benzol abdestilliert und das ausgefallene 1-Adamantylmalonsäuremonoäthylestermonochlorid (5,11 g, 96 %) wird üblicherweise aufgearbeitet.Example 2 1-Adamantylmalonic acid monoethyl ester monochloride For the solution of 5 g (0.0188 mol) of 1-adamantylmalonic acid monoethyl ester in 50 ml of dry benzene 5 ml (0.069 mol) of thionyl chloride are gradually added dropwise and the reaction solution is heated for 90 minutes at 600C. Then benzene is distilled off and the precipitated 1-Adamantylmalonic acid monoethyl ester monochloride (5.11 g, 96%) is commonly used worked up.
Beispiel 3 α-Carbonamido-1-adamantylessigsäureäthylester 5 g 1-Adamantylmalonsäuremonoäthylestermonochlorid wird in 50 ml trockenem Methylenchlorid gelöst, die Lösung abgekühlt und unter Ren trockenes Ammoniakgas 40 minuten bei Go 0 eingeleitet. Der ausgefallene Niederschlag wird abfiltriert und das Lösungsmittol aus dem Filtrat abdestilliert. Man erhält den Niederschlag (3,87 g, 84 %) des α-Carbonamido-1-adamantylessigsäureäthylesters, Schmp. 136-138°C. Das Produkt kann aus Chloroform-Petroläther umkristallisiert werden und weist den Schmelzpunkt von 138-140°C auf.Example 3 α-Carbonamido-1-adamantyl acetic acid ethyl ester 5 g 1-Adamantylmalonsäuremonoäthylestermonochlorid is dissolved in 50 ml of dry methylene chloride dissolved, the solution cooled and under Ren dry ammonia gas for 40 minutes Go 0 initiated. The deposited precipitate is filtered off and the solvent distilled off from the filtrate. The precipitate (3.87 g, 84%) of the α-carbonamido-1-adamantyl acetic acid ethyl ester is obtained, M.p. 136-138 ° C. The product can be recrystallized from chloroform petroleum ether and has a melting point of 138-140 ° C.
Beispiel 4 a-Amino-1 adamantylessigsäure In 5 ml Natriumhypochlorit-tösung (10,3 g NaOCl/100 ml -0,00694 Ml) wird unter Kühlung 0,278 g (0,00694 Mol) Natriumlauge gelöst. Zu dieser Lösung wird 1 g (0,00377 Mol) α-Carbonamido-1-adamantylessigsäureäthylester, der in 20 ml Wasser suspendiert ist, und 20 ml 0,5 N Natriumlauge zugefügt und das Reaktionsgemisch wird eine Stunde bei Siedetemperatur erhitzt. Nach der Abkthlung wird das Reaktionsgemisch filtriert, das Filtrat wird mit Chlorwasserstoffsäure auf pH 5,6 angesäuert, wobei als Niederschlag die a-Amino-1-adamantylessigsäure mit Schmp. 262-264°C (in zugeschmolzenem Röhrchen) ausgeschieden wird.Example 4 α-Amino-1 adamantylacetic acid In 5 ml of sodium hypochlorite solution (10.3 g NaOCl / 100 ml -0.00694 Ml) is 0.278 g (0.00694 mol) sodium hydroxide solution with cooling solved. To this solution 1 g (0.00377 mol) of α-carbonamido-1-adamantyl acetic acid ethyl ester, which is suspended in 20 ml of water, and 20 ml of 0.5 N sodium hydroxide solution added and that The reaction mixture is heated at boiling temperature for one hour. After cooling off the reaction mixture is filtered, the filtrate is treated with hydrochloric acid acidified to pH 5.6, the precipitate being the α-amino-1-adamantylacetic acid with melting point 262-264 ° C (in a sealed tube) is excreted.
Claims (5)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| YU311674A YU36150B (en) | 1974-11-22 | 1974-11-22 | Process for preparing alpha-amino-1-adamantyl acetic acid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE2551728A1 true DE2551728A1 (en) | 1976-05-26 |
Family
ID=25559366
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19752551728 Withdrawn DE2551728A1 (en) | 1974-11-22 | 1975-11-18 | PROCESS FOR PRODUCTION OF ALPHA-AMINO-1-ADAMANTYLACETIC ACID |
Country Status (4)
| Country | Link |
|---|---|
| AT (1) | AT338756B (en) |
| CH (1) | CH614695A5 (en) |
| DE (1) | DE2551728A1 (en) |
| YU (1) | YU36150B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997033859A1 (en) * | 1996-03-14 | 1997-09-18 | Warner-Lambert Company | Novel bridged cyclic amino acids as pharmaceutical agents |
-
1974
- 1974-11-22 YU YU311674A patent/YU36150B/en unknown
-
1975
- 1975-11-18 DE DE19752551728 patent/DE2551728A1/en not_active Withdrawn
- 1975-11-19 CH CH1501875A patent/CH614695A5/en not_active IP Right Cessation
- 1975-11-20 AT AT882675A patent/AT338756B/en not_active IP Right Cessation
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997033859A1 (en) * | 1996-03-14 | 1997-09-18 | Warner-Lambert Company | Novel bridged cyclic amino acids as pharmaceutical agents |
| US6020370A (en) * | 1996-03-14 | 2000-02-01 | Warner-Lambert Company | Bridged cyclic amino acids as pharmaceutical agents |
Also Published As
| Publication number | Publication date |
|---|---|
| YU311674A (en) | 1981-06-30 |
| CH614695A5 (en) | 1979-12-14 |
| YU36150B (en) | 1982-02-25 |
| ATA882675A (en) | 1977-01-15 |
| AT338756B (en) | 1977-09-12 |
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