DE1670268A1 - Tropic acid esters and process for their preparation - Google Patents
Tropic acid esters and process for their preparationInfo
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- DE1670268A1 DE1670268A1 DE19671670268 DE1670268A DE1670268A1 DE 1670268 A1 DE1670268 A1 DE 1670268A1 DE 19671670268 DE19671670268 DE 19671670268 DE 1670268 A DE1670268 A DE 1670268A DE 1670268 A1 DE1670268 A1 DE 1670268A1
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- ester
- acid ester
- tropic acid
- optionally branched
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
- C07D213/30—Oxygen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/20—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
- C07D211/22—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms by oxygen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/40—Oxygen atoms
- C07D211/42—Oxygen atoms attached in position 3 or 5
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
- C07D211/46—Oxygen atoms attached in position 4 having a hydrogen atom as the second substituent in position 4
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—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
- C07D295/04—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 with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—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 with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/084—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 with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/088—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 with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
Description
Tropasäureester und Verfahren zu ihrer Herstellung Die Erfindung betrifft ein neues Verfahren zur Herstellung von Tropasäureestern der allgemeinen Formel sowie ihrer Quaternierungsprodukte.Tropic acid esters and process for their preparation The invention relates to a new process for the preparation of tropic acid esters of the general formula as well as their quaternization products.
In der Formel 1 wie auch im folgenden bedeutet R1 ein Wasserstoffatom oder einen Acylrest ; Ra bezeichnet die Gruppe worin n für 1, 2 oder 3 steht, oder die Gruppe worin A eine gegebenenfalls verzweigte aliphatische Kohlenstoffkette mit mindestens 2 Kohlenstoffatomen bezeichnet, wobei das Sauerstoff-und das Stickstoffatom n C. ; t mit demselben Kohlenstoffatom verknüpft sind ; R und R', die gleich oder-verschieden sein können, stehen für unverzweigte oder verzweigte gesättigte oder ungesättigte aliphatische Reste, vorzugsweise für niedere bis mittlere Alkylreste, oder für Cycloalkylreste mit vorzugsweise 3 bis 7 Kohlenstoffatomen ; R und R@ können auch gemeinsam für einen gegebenenfalls verzweigten und/oder durch ein Heteroatom unterbrochenen Alkylenrest mit 4 bis 6 Kettengliedern stehen ; R karen ferner einen gegebenenfalls verzweigten und/oder durch ein Heteroatom unterbrochenen Alkylenrest bedeuten, der mit dem Stickstoffatom und einem Kohlenstoffatom von A zu einem 5-, 6- oder 7-gliedrigen heterocyelischen Ring verknüpft ist.In formula 1 and also below, R1 denotes a hydrogen atom or an acyl radical; Ra denotes the group wherein n is 1, 2 or 3, or the group wherein A denotes an optionally branched aliphatic carbon chain with at least 2 carbon atoms, the oxygen and nitrogen atoms n C.; t are linked to the same carbon atom; R and R ', which can be identical or different, stand for unbranched or branched, saturated or unsaturated aliphatic radicals, preferably for lower to medium alkyl radicals, or for cycloalkyl radicals with preferably 3 to 7 carbon atoms; R and R @ can also together represent an optionally branched and / or interrupted by a heteroatom alkylene radical with 4 to 6 chain members; R can also denote an optionally branched and / or interrupted by a heteroatom alkylene radical which is linked to the nitrogen atom and a carbon atom of A to form a 5-, 6- or 7-membered heterocyclic ring.
Die Verbindungen der Formel I werden hergestellt, indem man einen Alkohol der Formel R ? H mit einem a-Formylphenylessigsäureester, vorzugsweise dem Ester eines niederen aliphatischen Alkohols, umestert, den erhaltenen a-Formylphenylesaigaäureester der Formel mit einem Hetallborhydrid, vorzugsweise einem Alkaliborhydrid, reduziert und gewünschtenfalls zur Herstellung solcher Verbindungen der Formel I, in denen R1 einer. Acylrest bezeichnet, anschließend nach üblichen Methoden acyliert und/oder quaterniert.The compounds of the formula I are prepared by adding an alcohol of the formula R? H with an α-formylphenyl acetic acid ester, preferably the ester of a lower aliphatic alcohol, transesterified, the resulting a-formylphenyl acetic acid ester of the formula with a metal borohydride, preferably an alkali borohydride, reduced and, if desired, for the preparation of those compounds of the formula I in which R1 is one. Acyl radical, then acylated and / or quaternized by customary methods.
Das erfindungsgemä#e Verfahren verläuft überraschend glatt und liefert die Verbindungen der Formel I in hohen ausbeuten.The process according to the invention runs surprisingly smoothly and delivers the compounds of formula I in high yield.
Die Reduzierung eines a-For-, na3-lich des Tropinesters, ist bereits bekannt (deutsche Auslegeschrift 1 102 166). Jedoch werden gemä# dem Verfahren der DAS, das in der katalytischen Hydrierung desEstersunerDruckbestehr,zurReduzierungvon1 Ester 60 g Raney-Nickel aufgewende. Auch is-c die Ausbeute nur mä#ig.The reduction of an a-form, of course the tropine ester, is already known (German Auslegeschrift 1 102 166). However, according to the procedure of DAS, which is used in the catalytic hydrogenation of the Esteruner Druckbest, to reduce 1 Ester spend 60 g of Raney nickel. Also the yield is only moderate.
Das erfindungsgemä#e Verfahren wird im einzelnen folgenãerma3en durchgeführt.DieerseSufebesteh-cinderUmsetzung des Alkohols R H mit einem Formylphenylessigsäurealkylester, z. B. dem Methylester, Diese Umsetzung erfolgt vorzugsweise bei Temperaturen zwischen 100 und 140°C und unter Verwendung eines inerte Lösungsmittels wie Toluol oder Xylol. Als Umesterungskatalysator dient einer der-für diesen Jweck üblichen Katalysatoren, z.B. Natriummethylat.The method according to the invention is carried out in detail as follows. The stage consists of implementation of the alcohol R H with an alkyl formylphenylacetate, z. B. the methyl ester, This reaction is preferably carried out at temperatures between 100 and 140 ° C and using an inert solvent such as toluene or xylene. The transesterification catalyst used is one of the catalysts customary for this purpose, e.g. sodium methylate.
Als zweite Stufe erfolgt die Reduktion der a-Formylphenylessigsäureester mit Metallborhydriden, vorzugsweise Alkaliborhydriden, Die Reduktion wird vorzugsweise bei Raumtemperatur in Gegenwart eines geeigneten Lösungsmittels (Wasser, Methylenohlorid Methanol, Athanol, Ather, Benzol) oder eines Gemischs solcherLösungsmittelvorgenommen, als Reduktionsmittel wird zweckmä#ig Natriumborhydrid benutzt.The second stage is the reduction of the α-formylphenylacetic acid ester with metal borohydrides, preferably alkali borohydrides, The reduction is preferred at room temperature in the presence of a suitable solvent (water, methylene chloride Methanol, ethanol, ether, benzene) or a mixture of such solvents, Sodium borohydride is expediently used as a reducing agent.
Soll eine Verbindung der Formel 1 hergestellt werden, in der R1 einen Acylrest bedeutet, so wird anschlie#end nach üblichen Methoden acyliert. Werden als Endprodukte quarernäre Verbindungen gewünscht, so setzt man zuletzt die entsprechende Verbindung der Formel I mit einem üblichen entsprechenden Quaternisierungsmittel um, z.B. mit einem Halogenalkan, insbesondere Bromalkan.If a compound of the formula 1 is to be produced in which R1 is a Acyl radical means acylation is then carried out by customary methods. Will If quarernary compounds are desired as end products, then the appropriate one is added last Compound of the formula I with a customary corresponding quaternizing agent around, for example, with a haloalkane, especially bromoalkane.
Die Herstellung bisher nicht beschiriebener Ausgangsstoffe des Verfahrens erfolgt nach üblichen Methoden.The production of raw materials for the process not previously described takes place according to the usual methods.
Die N-substituierten Aminoalkanole werden duron Umsetzung der entsprechenden Amlne mit Äthylenoxid oder Äthyle chlorhydrin hergestellt (K. Krassusky, K. Kossenko, J. pr. Ohem. [2] 326 (1927) ; RB. Moffett, J. L. White, B D. Aspergren, F. E. Vits., J. Am. Chem. Sec. 77, 1565 (1955)).The N-substituted aminoalkanols are duron implementation of the corresponding Amine made with ethylene oxide or ethyl chlorohydrin (K. Krassusky, K. Kossenko, J. pr. Ohem. [2] 326 (1927); RB. Moffett, J. L. White, B. D. Aspergren, F. E. Vits., J. Am. Chem. Sec. 77, 1565 (1955)).
Die erfindungsgemäBen neuen Verbindungen sind wertvolle Pharmazeutika. Sie zeigen insbesondere spasmolytische Wirkung.The new compounds according to the invention are valuable pharmaceuticals. In particular, they show a spasmolytic effect.
Zur therapeutischen Anwendung werden sie mit den in der galenischen Pharmazie üblichen Hilfs- und Trägerstoffen su Tabletten, Dragees, Kapseln, Z Losungen usw. verarbeitet.For therapeutic use, they are used with the galenic Usual pharmaceutical auxiliaries and excipients such as tablets, coated tablets, capsules, Z solutions etc. processed.
Die folgenden Beispiele sollen die Erfindung näher erläuterno Beispie 1 1 Tropasäureester-N-ß-hydroxyäthylpiperidin a) α-Formylphenylessigsäureester-N-ß-hydroxyäthylpiperidin Zu einer siedenden Suspension von 500 mg Nabriusaethylat in 250 ccm absolutem Toluol laßt man unter Rühren innerhalb 6-Stunden gleichzeitig eine Lösung von 43,8 @g (0, 34 Mol) N-ß-Hydroxyäthlpiperidin iri 250 ccm absolutem Toluol und 79, 0 g (0, 44 Mol) kristallinem α-Formylphenylessigsaure-nethylester in 250 ccm Toluol so zutropfen, da# das gleiche Volumen eines Toluol-Methanol-Ge@isches abdestillierb, tAnschlie3end erhitzt man noch 1 Stunde unter schwachen. Ruckfluß. Die Reaktionslösung wird eingeeng'c-undderRückstandaitAceton-Petrolätherverses''.-* Der beim Anreiben auskristallisierende Ester wird abge@ saugt und getrocknet.The following examples are intended to explain the invention in more detail Example 1 1 tropic acid ester-N-ß-hydroxyethylpiperidine a) α-formylphenylacetic acid ester-N-ß-hydroxyethylpiperidine To a boiling suspension of 500 mg of nabrius ethylate in 250 ccm of absolute toluene let a solution of 43.8 @g (0, 34 mol) of N-ß-Hydroxyäthlpiperidin in 250 ccm of absolute toluene and 79.0 g (0.44 Mol) crystalline methyl α-formylphenyl acetic acid in 250 ccm of toluene so add dropwise, that the same volume of a toluene-methanol Ge @ isches distill off, Then the mixture is heated for 1 hour under weak. Reflux. The reaction solution is narrowed-and the residue is acetone-petroleum ether verses '' The ester that crystallizes out is filtered off with suction and dried.
Ausbeute 23,0 g (24, 6 % d.Th.) ; farblose Kristalle aus Aoeton,.146-147°C.-"-"'-ü?.-'. b) Tropasäureeser--S-hydroyäthyTpiperidih'"'-'--' Kan suspendiere 23, 0 g (0,084 Mol) des nach a) dargestellten Formylesters in einer Mischung von 240 ccm Methylenchlorid und 64 ccm Wasser und gibt unter kräftigem Rühren bei Raumtemperatur innerhalb einer Stunde 3,78 @g (0,1 Mol) Natriumborhydrid in kleinen Portionen zu. Der Formylester geht mit fortschreitender Reduktion allmählich in Lösung. Anschlie#end wird eine Stunde nachgerührt. Yield 23.0 g (24.6% of theory); colorless crystals from aoeton, .146-147 ° C .- "-" '- ü? .-'. b) Tropic acideser - S-hydroyäthyTpiperidih '"' -'-- 'Kan suspend 23.0 g (0.084 Mol) of the formyl ester prepared according to a) in a mixture of 240 cc of methylene chloride and 64 cc of water and gives with vigorous stirring at room temperature within a Hour 3.78 g (0.1 mol) sodium borohydride in small portions. The formyl ester gradually dissolves as the reduction progresses. Then a Stirred for an hour.
Die organische Phase wird abgetrennt, die wä#rige Phase dreimal mit je 20 ccm Methylenchlorid gewaschen und die vereinigten organischen Auszüge über Natriumsulfat getrocknet. Nach dem Einengen im Vakuum erhält man 19,7 g (71, 0 % d. Th.) eines dünnflüssigen gelben Ö les.The organic phase is separated off, the aqueous phase with three times washed 20 ccm of methylene chloride and the combined organic extracts over Dried sodium sulfate. After concentration in vacuo, 19.7 g (71.0% d. Th.) Of a thin yellow oil.
Das in iibliciler Weise dargestellte neutrale Cxalat schnilzt bei 118-119°C (aus Acetonitril).The neutral Cxalat, represented in the usual way, snaps at 118-119 ° C (from acetonitrile).
Folgende Verbindungen wurden nach diesem Verfahren bzw. aus ihnen durch Quaternierung nach bekannten Verfahren hersestellt : Tropasäureester-N-ß-hydroxyäthylpiperidin-brom-methylat, farbloses Kristalle aus Isobutanol, Fp. 121-123°C ; Tropasäureester-N-ß-hydroxyäthlpiperidin-brom-hexylat, farblose Kristalle aus Aceton-Isopropyldther, Fp. 106-108°C, Tropasäureester-N-ß-hydroxyäthylpiperidin-brom-heptylat, farblose Kristalle aus Aceton-Essigester, Fp. 117-119°C; Tropasäureester-N-ß-hydroxyäthylpiperidin-brom-octylat, farblose Kristalle aus Aceton-Essigester, Fp. 110-112°C; Tropasäureester-N-ß-hydroxyäthylpiperidin-brom-nonylat, farblose Kristalle aus Aceton-Essigester, Fp. 92-94°C; α-Formylphenylessigsäureester-N-ß-hydroxyäthylmorpholin, liellgelbe Kristalle aus Methanol, Fp 96-98°C ; Tropasäureester-N-B-hydroxyäthylmorpholin-oxalat, farblose Kristalle aus Acetonitril, Fp. 118-120°C ; a-Formylphenylessigsäureester-N-ß-hydroxyäthylpyrrolidin, hellgelbe Kristalle, Fp. 135-137°C ; α-Formylphenylessigsäureester-N-ß-hydroxyäthylhexamethylenimin, hellgelbe Kristalle, Fp. 123-125°C ; Durch Reduktion mit Natriunborhydrid nach Ib) wurde hieraus der Tropasäureester als hellgelbes Öl gewonnen ; er wird als Rohprodukt zu-den Quaternierungen eingesetzt.The following compounds were made by or from this process produced by quaternization according to known processes: tropic acid ester N-ß-hydroxyethylpiperidine bromomethylate, colorless crystals from isobutanol, melting point 121-123 ° C .; Tropic acid ester-N-ß-hydroxyäthlpiperidin-bromo-hexylat, colorless crystals from acetone-isopropyl ether, melting point 106-108 ° C, tropic acid ester-N-ß-hydroxyethylpiperidine bromoheptylate, colorless crystals from acetone-ethyl acetate, melting point 117-119 ° C .; Tropic acid ester-N-ß-hydroxyethylpiperidine-bromo-octylate, colorless crystals of acetone-ethyl acetate, melting point 110-112 ° C; Tropic acid ester-N-ß-hydroxyethylpiperidine-bromononylate, colorless crystals from acetone / ethyl acetate, melting point 92-94 ° C; α-Formylphenylacetic acid ester-N-ß-hydroxyethylmorpholine, slightly yellow crystals from methanol, mp 96-98 ° C; Tropic acid ester-N-B-hydroxyethylmorpholine-oxalate, colorless crystals from acetonitrile, melting point 118-120 ° C .; a-Formylphenylacetic acid ester-N-ß-hydroxyethylpyrrolidine, light yellow crystals, m.p. 135-137 ° C; α-Formylphenylacetic acid ester-N-ß-hydroxyethylhexamethyleneimine, light yellow crystals, m.p. 123-125 ° C; By reduction with sodium borohydride according to Ib) The tropic acid ester was obtained from this as a light yellow oil; it is used as a raw product used to-the quaternations.
Tropasäureester-N-ß-hydroxyäthylhexamethyleninin-brommethylat, farblose. Kristalle aus Isopropanol, Fp. 151-152, 5°C ; Tropasäureester-N-ß-hydroxyäthylhexamethylenimin-bromhexylat, farblose Kristalle aus Acetonitril, Fp. 137-139°C ; Tropasäureester-N-ß-hydroxyäthylhexamethylenimin-bromheptylat, farblose Kristalle aus Acetonitril, Fp. 158-160°C ; Tropasäureester-N-ß-hydroxyäthylhexamethylenimin-bromo c tyla-t farblose Kristalle aus Isobutanol, Fp. 148-150°C; Tropasäureester-N-ß-hydroxyäthylhexamethylenimin-bromnonylab, farblose Kristalle aus Acetonitril, Fp. 115-117°C; α-Formylphenylessigsäureester-dimethylaminoäthanol, farblose Kristalle aus Aceton-Petroläther, Fp. 128-131°C.Tropic acid ester-N-ß-hydroxyethylhexamethyleneinine bromomethylate, colorless. Crystals from isopropanol, m.p. 151-152, 5 ° C; Tropic acid ester-N-ß-hydroxyethylhexamethyleneimine-bromohexylate, colorless crystals from acetonitrile, mp 137-139 ° C; Tropic acid ester-N-ß-hydroxyethylhexamethyleneimine bromheptylate, colorless crystals from acetonitrile, melting point 158-160 ° C .; Tropic acid ester-N-ß-hydroxyethylhexamethyleneimine-bromo c tyla-t colorless crystals from isobutanol, melting point 148-150 ° C; Tropic acid ester-N-ß-hydroxyethylhexamethyleneimine-bromnonylab, colorless crystals from acetonitrile, mp 115-117 ° C; α-formylphenyl acetic acid ester dimethylaminoethanol, colorless crystals from acetone-petroleum ether, melting point 128-131 ° C.
Durch Reduktion mit Natriumborhydrid nach lb) wurdehieraus der Tropasäureester also hellgelbes Öl gewonnen; er wird al ; @ Rohproduk t zu den Quaternierungen eingesetzt.The tropic acid ester was converted into this by reduction with sodium borohydride according to Ib) thus obtained light yellow oil; he will al; @ Raw product used for the quaternization.
Tropasäureester-dimethylaminoäthanol-brom-methylat, im aus ilceboni-bril, Tropasäureester-dimethylaminoäthanol-brom-äthyles, far@@@@@ Kristalle aus Acztonitril, Ep. 134-136@@ Tropasäureester-dimethylaminoäthanol-brom-propy@@@@, Trop. s''.r:;esbr-diNebhylaaiuoäthan.ol"bron]*-buCj'lM Tropasäureester-dimethylaminoäthanol-brom-butylat, teat.'iJjacG : .. flr'. : : : : e : "-LtvlF ? E.' CC. Le7 ; ft11i1C') : Lru"4. t.'a'l : ii'iii. t^^'I. is=, ox. t>R Tarblose Kristalle aus Acetonitril, Fp. 134-135°C; Tropasäureester-dimethylaminoäthanol-brom-hexylat, farblose Kristalle aus Aceonitril, Fp. 122-120 ; Tropasäureester-dimethylaminoäthanol-brom-heptylat, farblose KristalleausAceon,?p.126-128C;'' Tropasäureester-dimethylaminoäthanol-brom=octylat, farbloseKristalleausAceton,Fpt126-126C,,;..-..-',.Tropic acid ester dimethylaminoethanol bromomethylate, im from ilceboni-bril, Tropic acid ester-dimethylaminoethanol-bromo-ethyl, far @@@@@ Crystals from Acztonitril, Ep. 134-136 @@ tropic acid ester-dimethylaminoethanol-bromopropy @@@@, Trop. s ''. r:; esbr-diNebhylaaiuoäthan.ol "bron] * - buCj'lM Tropic acid ester dimethylaminoethanol bromobutylate, teat.'iJjacG: .. flr '. ::: : e: "-LtvlF? E. ' CC. Le7; ft11i1C '): Lru "4. t.'a'l: ii'iii. t ^^ 'I. is =, ox. t> R Tarbless crystals from acetonitrile, melting point 134-135 ° C; Tropic acid ester dimethylaminoethanol bromohexylate, colorless crystals from aceonitrile, m.p. 122-120; Tropic acid ester dimethylaminoethanol bromoheptylate, colorless crystals of aceon,? p.126-128C; '' tropic acid ester-dimethylaminoethanol-bromine = octylate, colorless crystals of acetone, Fpt126-126C ,,; ..-..- ',.
Tropasäureester-dimethylaminoäthanol-brom-nonylat, farblose KrisballeausAceton,?,p.115-117"'n...-...-Tropasäureester-dimethylaminoäthanol-brom-decylat, farblose Kristalle aus Aceton, Fp- 128-129°C; Tropasäureester-dimethylaminoäthanol-brom-undecylat, farblose Kristalle aus Aceton, Fp. 129-130°C; 'Pro'pusäureester-disiehylaainoatha:iol-'brodD,dcO'la;... farbloseSrisCalla.us-.Aeeb.o:n,-p...L23p;.,j,.,...-;.-. ropasaurejster-3-hydroxyuebhyißyridL hellgelbeKristalleausAoecon,Fp,38-IOOJ.-; t c : asiiar ; : i : rf. =-... i. zc. u. ; F. r=iii. c-i ;-, : . °r : ~arv fartlose Kristalle aus Methanol, Fp. 103-105°C; Tropasäureester-4-hydroxymethylpyridin, a) α-Formylphenylessigsäureester-4-hydroxymethylpyridin, rosa Kristalle aus Aceton, Fp. 142-144°C; b) Tropasäureester-4-hydroxymethylpyridin-hydrochlorid farblose Kristalle aus Isobutanol, Fp. 151-153°C ; Tropasäureester-2-hydroxymethylpyridin, a) Fornylester Hellgelbe Kristalle aus Aceton, Fp. 92-94°C, durch Reduktion mit Natriumborhydrid nach 1b) wurde hieraus der Tropasaureester als hellgelbes Öl gewonnen ; er wird als Rohprodukt zur Quaternierung mit Methylbromid eingesetzt. b) Tropasäureester-2-hydroxymethylpyridin-brom-methylat, farblose Kristalle aus Isobutanol, Fp. 123-125°C; α-Formylphenylessigsäure-(N-methyl-4-hydroxymethylpiperidin)-ester), gelbe Kristalle aus Aceton, Pp. 157-159°C ; ~ AusbeuTe : 61, 8 % d. Th.Tropic acid ester dimethylaminoethanol bromononylate, colorless crystals of acetone,?, P.115-117 "'n ...-...- tropic acid ester dimethylaminoethanol bromodecylate, colorless crystals from acetone, mp 128-129 ° C; Tropic acid ester dimethylaminoethanol bromine undecylate, colorless crystals from acetone, m.p. 129-130 ° C; 'Pro'pusäureester-disiehylaainoatha: iol-'brodD, dcO'la; ... colorlessSrisCalla.us-.Aeeb.o: n, -p ... L23p;., j,., ...-; .-. ropasaurejster-3-hydroxyuebhyißyridL light yellow crystals of Aoecon, m.p. 38-100J.-; t c: asiiar; : i: rf. = -... i. zc. u.; F. r = iii. c-i; -,:. ° r: arv flare-free crystals from methanol, melting point 103-105 ° C .; Tropic acid ester-4-hydroxymethylpyridine, a) α-Formylphenylacetic acid ester-4-hydroxymethylpyridine, pink crystals from Acetone, m.p. 142-144 ° C; b) Tropic acid ester 4-hydroxymethylpyridine hydrochloride colorless Crystals from isobutanol, m.p. 151-153 ° C; Tropic acid ester-2-hydroxymethylpyridine, a) Fornylester Light yellow crystals from acetone, melting point 92-94 ° C, by reduction with Sodium borohydride according to 1b), the tropic acid ester was obtained from this as a light yellow oil ; it is used as a crude product for quaternization with methyl bromide. b) tropic acid ester 2-hydroxymethylpyridine bromomethylate, colorless crystals from isobutanol, melting point 123-125 ° C .; α-Formylphenylacetic acid (N-methyl-4-hydroxymethylpiperidine) ester), yellow crystals from acetone, bp 157-159 ° C; ~ Yield: 61.8% d. Th.
Tropasäure-(N-methyl-4-hydroxymethyl-piperidin)-esterhydrochlorid weiße Kristalle aus Isopropanol, Fp. 134-136°o ; Ausbeute : 66 % d.Th. Tropic acid (N-methyl-4-hydroxymethyl-piperidine) ester hydrochloride white crystals from isopropanol, m.p. 134-136 ° o; Yield: 66% of theory
Tropasäure- (N-methyl-4-hydroxymethyl-piperidin)-esterbrom-methylat, < weiße Kristalle aus Acetonitril, Fp. 123-125°C ; Ausbeute : 52,2 % d. Th. ; a-Formylphenylessigsäure- (N-methyl-3-hydroxymethylpiperidin)-ester, gelbe Kristalle aus Aceton, Fp. 143-145°C; Ausbeute : 69, 3 % d. Th.Tropic acid (N-methyl-4-hydroxymethyl piperidine) ester bromomethylate, <white crystals from acetonitrile, melting point 123-125 ° C; Yield: 52.2% of theory Th.; α-Formylphenylacetic acid (N-methyl-3-hydroxymethylpiperidine) ester, yellow crystals from acetone, m.p. 143-145 ° C; Yield: 69.3% of theory Th.
Tropasäure- (N-methyl-3-hydroxymethyl-piperidin)-esterhydrochlorid, weiße Kristalle aus Acetonitril, Fp. 177-179°C; Ausbeute : 14 % d.. Th. ; Tropasäure-(N-methyl-3-hydroxymethyl-piperidin)-esterbrom-methylat, weiße Kristalle aus Alkohol, Fp. 126-127°C ; Ausbeute : 52, 2 % d. Th. ; a-Formylphenylessigsäure- (N-methyl-3-hydroxy-pip'eridin)-ester, Kp0,01 128-135°C Tropasäure- (N-methyl-3-hydroxy-piperidin)-ester-hydrochlorid,/ wei#e Kristalle aus Methylaethylketon, Fp. 127-128°C; Ausbeute : 32,8 % d.Th. ; i-Bormylphenylessigsäure-(N-methyl-4-hydroxy-piperidin)-ester Tropasäure-(N-methyl-4-hydroxy-piperidin)-ester-hydrochlorid, weiBe Kristalle aus Isopropanol, Fp. 161-162°C ; Tropasäure-(N-methyl-4-hydroxy-piperidin)-ester-bromisopropylat, wei#e Kristalle aus Alkohol, Fp. 203°C ; Ausbeu. te : 36, 4 % d. Th. ; a-Formylphenylessigsäure- (N-aethyl-4-hydroxy-piperidin)-ester, gelbe Kristalle au. s olu. ol Fp. 173-174°C ; Au. sbeute : 80, 7 % d. Th. ; Tropasäure-(N-aethyl-4-hydroxy-piperidin)-esterhydrochlorid-,-"'-weiße Kristalle au. s Methylaethylketon Fp. 139-140°C ; Ausbeute : 80, 7 % d. Th.Tropic acid (N-methyl-3-hydroxymethyl-piperidine) ester hydrochloride, white crystals from acetonitrile, m.p. 177-179 ° C; Yield: 14% of theory; Tropic acid (N-methyl-3-hydroxymethyl-piperidine) ester bromomethylate, white crystals from alcohol, m.p. 126-127 ° C; Yield: 52.2% of theory. Th.; a-formylphenylacetic acid (N-methyl-3-hydroxy-piperidine) ester, bp 0.01 128-135 ° C tropic acid (N-methyl-3-hydroxy-piperidine) ester hydrochloride, / white crystals from methyl ethyl ketone, melting point 127-128 ° C .; Yield: 32.8% of theory ; i-Bormylphenylacetic acid (N-methyl-4-hydroxypiperidine) ester Tropic acid (N-methyl-4-hydroxypiperidine) ester hydrochloride, white crystals Isopropanol, m.p. 161-162 ° C; Tropic acid (N-methyl-4-hydroxypiperidine) ester bromoisopropoxide, white crystals from alcohol, melting point 203 ° C .; Stress te: 36.4% d. Th.; a-formylphenylacetic acid (N-ethyl-4-hydroxypiperidine) ester, yellow crystals au. s olu. ol m.p. 173-174 ° C ; Au. Yield: 80.7% of theory Th.; Tropic acid (N-ethyl-4-hydroxypiperidine) ester hydrochloride -, - "'- white Crystals au. s methyl ethyl ketone mp 139-140 ° C; Yield: 80.7% of theory Th.
α-Formylphenylessigsäure-(N-isopropyl-4-hydroxy-piperidin)-ester, gelbe Kristalle aus Toluol, Fp. 171-173°C ; Ausbeute : 61, 2 % d. Th. ; ropasäure-(N-isopropyl-4-hydroxy-piperidin)-esterhydrochlorid,-weiße Kristalle aus Aceton, Fp. 160-162°C ; Ausbeute : 76, 4 % d.Th.; Tropasäure- (N-isopropyl-4-hydroxy-piperidin)-ester-brommethylat, wei#e Kristalle aus Aaetonitril, Fp. 173-182°C; Ausbeute : 79, 8 % d. Th. ; α-Formylphenylessigsäure-(N-butyl-4-hydroxypiperidin)-ester, gelbe Kristalle aus Toluol, Fp. 157-158°C; Ausbeute : 78, 5 % d. Th. ; Tropasäure- (N-butyl-4-hydroxy-piperidin)-ester-hydrochlorid, weiße Kristalle aus Acetonitril, Fp. 126-127°C; Ausbeute : 73,5 % d.Th. ; Tropasäure- (N-butyl-4-hydroxy-piperidin)-ester-brommethylat, weiße Kristalle aus Acetonitril, Fp. 171-173°C; Ausbeute texα-Formylphenylacetic acid (N-isopropyl-4-hydroxypiperidine) ester, yellow crystals from toluene, m.p. 171-173 ° C; Yield: 61.2% of theory Th.; ropic acid (N-isopropyl-4-hydroxypiperidine) ester hydrochloride, white Crystals from acetone, m.p. 160-162 ° C; Yield: 76.4% of theory; Tropic acid (N-isopropyl-4-hydroxypiperidine) ester bromomethylate, white crystals from acetonitrile, melting point 173-182 ° C .; Yield: 79.8% of theory Th.; α-Formylphenylacetic acid (N-butyl-4-hydroxypiperidine) ester, yellow crystals from toluene, m.p. 157-158 ° C; Yield: 78.5% of theory Th.; Tropic acid (N-butyl-4-hydroxypiperidine) ester hydrochloride, white crystals from acetonitrile, Mp 126-127 ° C; Yield: 73.5% of theory ; Tropic acid (N-butyl-4-hydroxypiperidine) ester bromomethylate, white crystals from acetonitrile, m.p. 171-173 ° C; Yield tex
Claims (3)
Priority Applications (8)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ES358028A ES358028A1 (en) | 1967-09-12 | 1968-09-11 | Tropic acid esters |
| BE720749D BE720749A (en) | 1967-09-12 | 1968-09-12 | |
| IL30693A IL30693A0 (en) | 1967-09-12 | 1968-09-12 | Novel esters of tropic acid,their preparation and pharmaceutical compositions containing them |
| AT890768A AT281024B (en) | 1967-09-12 | 1968-09-12 | Process for the production of new tropic acid esters and their quaternization products and salts |
| GB43511/68A GB1236962A (en) | 1967-09-12 | 1968-09-12 | Tropic acid esters |
| FR1589730D FR1589730A (en) | 1967-09-12 | 1968-09-12 | |
| CH1364168A CH514588A (en) | 1967-09-12 | 1968-09-12 | Process for the preparation of tropic acid esters and their use for the preparation of their quaternary compounds |
| FR177915A FR8308M (en) | 1967-09-12 | 1968-12-12 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEB0094421 | 1967-09-12 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE1670268A1 true DE1670268A1 (en) | 1970-08-13 |
Family
ID=6987566
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19671670268 Pending DE1670268A1 (en) | 1967-09-12 | 1967-09-12 | Tropic acid esters and process for their preparation |
Country Status (2)
| Country | Link |
|---|---|
| DE (1) | DE1670268A1 (en) |
| NL (1) | NL6812994A (en) |
-
1967
- 1967-09-12 DE DE19671670268 patent/DE1670268A1/en active Pending
-
1968
- 1968-09-11 NL NL6812994A patent/NL6812994A/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| NL6812994A (en) | 1969-03-14 |
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