NO117868B - - Google Patents
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- NO117868B NO117868B NO15715365A NO15715365A NO117868B NO 117868 B NO117868 B NO 117868B NO 15715365 A NO15715365 A NO 15715365A NO 15715365 A NO15715365 A NO 15715365A NO 117868 B NO117868 B NO 117868B
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- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 150000001408 amides Chemical class 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 150000004982 aromatic amines Chemical class 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 150000004820 halides Chemical class 0.000 claims description 2
- 125000000623 heterocyclic group Chemical group 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 125000003386 piperidinyl group Chemical group 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- 239000000243 solution Substances 0.000 description 17
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 150000001875 compounds Chemical class 0.000 description 10
- 239000003513 alkali Substances 0.000 description 9
- 239000003610 charcoal Substances 0.000 description 8
- 238000010992 reflux Methods 0.000 description 7
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- -1 piperidine monocarboxylic acid halide Chemical class 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hcl hcl Chemical compound Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- DENRZWYUOJLTMF-UHFFFAOYSA-N diethyl sulfate Chemical compound CCOS(=O)(=O)OCC DENRZWYUOJLTMF-UHFFFAOYSA-N 0.000 description 3
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- UFFBMTHBGFGIHF-UHFFFAOYSA-N 2,6-dimethylaniline Chemical compound CC1=CC=CC(C)=C1N UFFBMTHBGFGIHF-UHFFFAOYSA-N 0.000 description 2
- MLPVBIWIRCKMJV-UHFFFAOYSA-N 2-ethylaniline Chemical compound CCC1=CC=CC=C1N MLPVBIWIRCKMJV-UHFFFAOYSA-N 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- HXEACLLIILLPRG-YFKPBYRVSA-N L-pipecolic acid Chemical compound [O-]C(=O)[C@@H]1CCCC[NH2+]1 HXEACLLIILLPRG-YFKPBYRVSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- HXEACLLIILLPRG-RXMQYKEDSA-N l-pipecolic acid Natural products OC(=O)[C@H]1CCCCN1 HXEACLLIILLPRG-RXMQYKEDSA-N 0.000 description 2
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- ZGONCYGWELXUPA-AWEZNQCLSA-N (2S)-1-butyl-N-(2-chloro-6-methylphenyl)pyrrolidine-2-carboxamide Chemical compound ClC1=C(NC([C@H]2N(CCC2)CCCC)=O)C(=CC=C1)C ZGONCYGWELXUPA-AWEZNQCLSA-N 0.000 description 1
- VTVJMWZZVJSEMO-BYPYZUCNSA-N (2s)-pyrrolidine-2-carbonyl chloride Chemical compound ClC(=O)[C@@H]1CCCN1 VTVJMWZZVJSEMO-BYPYZUCNSA-N 0.000 description 1
- MPPPKRYCTPRNTB-UHFFFAOYSA-N 1-bromobutane Chemical compound CCCCBr MPPPKRYCTPRNTB-UHFFFAOYSA-N 0.000 description 1
- NAMYKGVDVNBCFQ-UHFFFAOYSA-N 2-bromopropane Chemical compound CC(C)Br NAMYKGVDVNBCFQ-UHFFFAOYSA-N 0.000 description 1
- WFNLHDJJZSJARK-UHFFFAOYSA-N 2-chloro-6-methylaniline Chemical compound CC1=CC=CC(Cl)=C1N WFNLHDJJZSJARK-UHFFFAOYSA-N 0.000 description 1
- KIHUWAOTZVYMFH-UHFFFAOYSA-N 4-butoxy-2,6-dimethylaniline Chemical compound CCCCOC1=CC(C)=C(N)C(C)=C1 KIHUWAOTZVYMFH-UHFFFAOYSA-N 0.000 description 1
- ZXPJSNYLHALLGL-UHFFFAOYSA-N CC(C=CC=C1C)=C1NC(C(CCCC1)N1C1CCCC1)=O Chemical compound CC(C=CC=C1C)=C1NC(C(CCCC1)N1C1CCCC1)=O ZXPJSNYLHALLGL-UHFFFAOYSA-N 0.000 description 1
- DSYFCRKFHZVMOS-UHFFFAOYSA-N CCCCOC(C=C1C)=CC(C)=C1NC(C1N(C)CCCC1)=O Chemical compound CCCCOC(C=C1C)=CC(C)=C1NC(C1N(C)CCCC1)=O DSYFCRKFHZVMOS-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- VUHKTERBGMWQAY-UHFFFAOYSA-N N-(2-ethylphenyl)-1-propan-2-ylpiperidine-3-carboxamide Chemical compound C(C)C1=C(NC(C2CN(CCC2)C(C)C)=O)C=CC=C1 VUHKTERBGMWQAY-UHFFFAOYSA-N 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 150000003931 anilides Chemical class 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- AQNQQHJNRPDOQV-UHFFFAOYSA-N bromocyclohexane Chemical compound BrC1CCCCC1 AQNQQHJNRPDOQV-UHFFFAOYSA-N 0.000 description 1
- BRTFVKHPEHKBQF-UHFFFAOYSA-N bromocyclopentane Chemical compound BrC1CCCC1 BRTFVKHPEHKBQF-UHFFFAOYSA-N 0.000 description 1
- 229940008406 diethyl sulfate Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- SRJOCJYGOFTFLH-UHFFFAOYSA-N isonipecotic acid Chemical compound OC(=O)C1CCNCC1 SRJOCJYGOFTFLH-UHFFFAOYSA-N 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 229960005015 local anesthetics Drugs 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- INWLQCZOYSRPNW-UHFFFAOYSA-N mepivacaine Chemical compound CN1CCCCC1C(=O)NC1=C(C)C=CC=C1C INWLQCZOYSRPNW-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 150000002762 monocarboxylic acid derivatives Chemical class 0.000 description 1
- AALBZAYEBOEAPQ-UHFFFAOYSA-N n-(2,6-dimethylphenyl)-1-ethylpiperidine-2-carboxamide Chemical compound CCN1CCCCC1C(=O)NC1=C(C)C=CC=C1C AALBZAYEBOEAPQ-UHFFFAOYSA-N 0.000 description 1
- DNZSDACGXYHMOL-UHFFFAOYSA-N n-(2-ethylphenyl)piperidine-3-carboxamide Chemical compound CCC1=CC=CC=C1NC(=O)C1CNCCC1 DNZSDACGXYHMOL-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
Classifications
-
- H—ELECTRICITY
- H04—ELECTRIC COMMUNICATION TECHNIQUE
- H04J—MULTIPLEX COMMUNICATION
- H04J3/00—Time-division multiplex systems
- H04J3/17—Time-division multiplex systems in which the transmission channel allotted to a first user may be taken away and re-allotted to a second user if the first user becomes inactive, e.g. TASI
Landscapes
- Engineering & Computer Science (AREA)
- Computer Networks & Wireless Communication (AREA)
- Signal Processing (AREA)
- Time-Division Multiplex Systems (AREA)
- Use Of Switch Circuits For Exchanges And Methods Of Control Of Multiplex Exchanges (AREA)
- Hydrogenated Pyridines (AREA)
Description
Fremgangsmåte til fremstilling av amider av N-alkylpiperidin-monokarbonsyre «g N-alkylpyrrolidin-«-monokarbonsyre. Process for the preparation of amides of N-alkylpiperidine-monocarboxylic acid «g N-alkylpyrrolidine-«-monocarboxylic acid.
Foreliggende oppfinnelse angår en The present invention relates to a
fremgangsmåte til fremstilling av amider method for the production of amides
av N-alkylpiperidin-monokarbonsyre og av of N-alkylpiperidine monocarboxylic acid and of
N-alkylpyrrolidin-a-monokarbonsyre, hvilke amider har de generelle formler: N-alkylpyrrolidine-α-monocarboxylic acid, which amides have the general formulas:
I disse formler betegner Ri en alkylgruppe, R- en lavere alkylgruppe eller et In these formulas Ri denotes an alkyl group, R- a lower alkyl group or et
kloratom, R:1 et hydrogenatom, en hydrok-sylgruppe, en lavere alkylgruppe eller en chlorine atom, R:1 a hydrogen atom, a hydroxyl group, a lower alkyl group or a
alkoksygruppe og Ra et hydrogenatom, et alkoxy group and Ra a hydrogen atom, et
kloratom, en lavere alkylgruppe eller en chlorine atom, a lower alkyl group or a
alkoksygruppe. Alternativt kan R2, R* og alkoxy group. Alternatively, R2, R* and
Ri alle være hydrogen i en og samme forbindelse. Karbonsyreamidgruppen kan væ-re tilknyttet piperidinringen i alfa-, beta-eller gamma-stillingen. Ri all be hydrogen in one and the same compound. The carboxylic acid amide group can be attached to the piperidine ring in the alpha, beta or gamma position.
Disse amider har vist seg å være meget These amides have been shown to be very
gode lokalanestetika med giftighet som er good local anesthetics with toxicity that is
meget liten i forhold til forbindelsenes very small compared to those of the compounds
aktivitet. Activity.
Ifølge oppfinnelsen fremstilles disse According to the invention, these are produced
forbindelser ved på kjent måte å la et pi-peridinmonokarbonsyrehalogenid eller et pyrrolidin-a-monokarbonsyrehalogenid eller et salt av en av disse forbindelser reagere med et aromatisk amin. Reaksjonen utføres fortrinsvis i et organisk oppløs-ningsmiddel og i nærvær av et overskudd av det aromatiske amin. Nitrogenatomet i den heterocykliske ring i det amid man får på denne måte alkylerer derpå under bruk av vanlige alkyleringsmidler. Det er bemer-kelsesverdig at kompliserende sidereaksjo-ner ikke inntreffer ved denne alkylering. compounds by allowing a piperidine monocarboxylic acid halide or a pyrrolidine α-monocarboxylic acid halide or a salt of one of these compounds to react with an aromatic amine in a known manner. The reaction is preferably carried out in an organic solvent and in the presence of an excess of the aromatic amine. The nitrogen atom in the heterocyclic ring in the amide obtained in this way is then alkylated using common alkylating agents. It is noteworthy that complicating side reactions do not occur with this alkylation.
De piperidin-mono- og pyrrolidin-«-monokarbonsyre-halogenider som er nød-vendig for denne reaksjon fremstilles hensiktsmessig ved å suspendere vedkommen-de syre eller dens hydroklorid i acetyl-klorid og å tilsette fosforpentaklorid til suspensjonen. Etter frafiltrering og vask-ning med et vannfritt oppløsningsmiddel er halogenet ferdig til bruk etter at det igjen er dispergert i et passende oppløs-ningsmiddel eller halogenidet kan tørres i vakuum og lagres. The piperidine mono- and pyrrolidine monocarboxylic acid halides necessary for this reaction are conveniently prepared by suspending the relevant acid or its hydrochloride in acetyl chloride and adding phosphorus pentachloride to the suspension. After filtering off and washing with an anhydrous solvent, the halogen is ready for use after it has been dispersed again in a suitable solvent or the halide can be dried in a vacuum and stored.
For terapeutisk formål brukes disse amider mest hensiktsmessig som salter med organiske eller anorganiske syrer, fortrinsvis som hydroklorider. For therapeutic purposes, these amides are most conveniently used as salts with organic or inorganic acids, preferably as hydrochlorides.
I det følgende beskrives som eksempler noen utførelsesformer for oppfinnelsen. In the following, some embodiments of the invention are described as examples.
Eksempel 1. Example 1.
170 vektdeler av hydrokloridet av pro-linklorid suspenderes i 100 deler aceton, hvorpå det tilsettes 350 deler 2-klor-6-me- 170 parts by weight of the hydrochloride of proline chloride are suspended in 100 parts of acetone, whereupon 350 parts of 2-chloro-6-me-
tylanilin. Denne tilsetning utføres raskt, og en nesten fullstendig oppløsning finner sted. Man holder reaksjonsatlandingen ko-kende i omkring 1/2 time hvorpå hydrokloridet av prolin-2-klor-6-metylanilid begyn-ner å krystallisere ut. Etter avkjøling frafiltreres bunnfallet og vaskes med aceton. For ytterligere rensning av bunnfallet opp-løses dette i vann, og oppløsningens pH-verdi innstilles på omkring 5,5 hvorpå den ekstraheres med et passende oppløsnings-middel, f. eks. eter, for å skille den led-sagende 2-klor-6-metylanilin fra oppløs-ningen. Etter fjernelse av oppløsningsmid-let behandles den tilbakeværende vandige oppløsning med trekull, og produktet utfelles med alkali. Bunnfallet frafiltreres og tørres i vakuum. 10 vektdeler av det herved erholdte rene prolin-2-klor-6-metyl-anilid oppløses i 2 volumdeler normal bu-tanol. Denne oppløsning tilsettes 5 vektdeler kaliumkarbonat og 5 deler normalt butylbromid, hvorpå man oppvarmer opp-løsningen under tilbakeløpskjøling og om-røring i 12 timer. Kaliumbromid fraskilles oppløsningen ved filtrering, og oppløsnin-gen inndampes til tørrhet. Residuet etter inndampningen oppløses i fortynnet saltsyre, behandles med trekull og felles påny med alkali. Det N-normalt-butylprolin-2-klor-6-metylanilid som utfelles herved er krystallinsk og er etter filtrering, vasking og tørring tilstrekkelig rent til å overføres til salter. tylaniline. This addition is carried out rapidly, and an almost complete dissolution takes place. The reaction mixture is kept boiling for about 1/2 hour, after which the hydrochloride of proline-2-chloro-6-methylanilide begins to crystallize out. After cooling, the precipitate is filtered off and washed with acetone. For further purification of the precipitate, this is dissolved in water, and the solution's pH value is set to around 5.5, after which it is extracted with a suitable solvent, e.g. ether, to separate the corresponding 2-chloro-6-methylaniline from the solution. After removal of the solvent, the remaining aqueous solution is treated with charcoal, and the product is precipitated with alkali. The precipitate is filtered off and dried in a vacuum. 10 parts by weight of the pure proline-2-chloro-6-methylanilide thus obtained are dissolved in 2 parts by volume of normal butanol. 5 parts by weight of potassium carbonate and 5 parts of normal butyl bromide are added to this solution, after which the solution is heated under reflux and stirring for 12 hours. Potassium bromide is separated from the solution by filtration, and the solution is evaporated to dryness. The residue after evaporation is dissolved in dilute hydrochloric acid, treated with charcoal and combined again with alkali. The N-normal-butylproline-2-chloro-6-methylanilide which is precipitated here is crystalline and, after filtration, washing and drying, is sufficiently pure to be transferred to salts.
Eksempel 2. Example 2.
184 vektdeler av pipekolinsyreklorid-hydroklorid bringes til å reagere med 363 deler 2,6-dimetylanilin på en måte lignen-de den i eksempel 1 beskrevne. Man får herved pipekolinsyre-2,6-dimetylanilid. Til 10 deler av denne forbindelse tilsettes 20 deler dietylsulfat, og blandingen holdes på dampbad i 3 timer. Etter nedkjøling til romtemperatur tilsettes 40 deler vann, og overskuddet av dietylsulfat ekstraheres ved hjelp av et passende oppløsningsmid-del, f. eks. eter. Etter at oppløsningen er befridd fra oppløsningsmiddel og dietylsulfat, behandles den med trekull og felles med alkali. Herved utfelles N-etyl-pipeko-linsyre-2,6-dimetylanilid i krystallinsk form. Bunnfallet frafiltreres, vaskes og tørres. 184 parts by weight of pipecolic acid chloride-hydrochloride are reacted with 363 parts of 2,6-dimethylaniline in a manner similar to that described in example 1. This gives pipecolic acid-2,6-dimethylanilide. To 10 parts of this compound, 20 parts of diethyl sulphate are added, and the mixture is kept on a steam bath for 3 hours. After cooling to room temperature, 40 parts of water are added, and the excess of diethyl sulphate is extracted using a suitable solvent, e.g. ether. After the solution is freed from solvent and diethyl sulfate, it is treated with charcoal and combined with alkali. This precipitates N-ethyl-pipecolic acid-2,6-dimethylanilide in crystalline form. The precipitate is filtered off, washed and dried.
Eksempel 3. Example 3.
10 vektdeler pipekolinsyre-2,6-dimetyl-anilid fremstillet som beskrevet i eksem- 10 parts by weight of pipecolic acid-2,6-dimethylanilide prepared as described in example
pel 2 oppløses i 20 volumdeler metanol, og pel 2 is dissolved in 20 parts by volume of methanol, and
oppløsningen tilsettes 10 vektdeler dimetylsulfat. Oppløsningen oppvarmes derpå under tilbakeløpskjøling i 10 timer hvorpå metanolen avdestilleres i vakuum. Bunnfallet oppløses i 40 deler vann og felles 10 parts by weight of dimethylsulphate are added to the solution. The solution is then heated under reflux for 10 hours, after which the methanol is distilled off in a vacuum. The precipitate is dissolved in 40 parts water and collected
med alkali. Den utfelte base, som i begyn-nelsen er tilbøyelig til å utfelles som en olje som senere krystalliserer, frafiltreres og vaskes. Uten å tørres oppløses derpå for-bindelsen i fortynnet saltsyre, behandles med trekull, utfelles påny, filtreres og vaskes. På denne måte får man krystallinsk N-metyl-pipekolinsyre-2,6-dimetylanilid. with alkali. The precipitated base, which initially tends to precipitate as an oil which later crystallizes, is filtered off and washed. Without drying, the compound is then dissolved in dilute hydrochloric acid, treated with charcoal, precipitated again, filtered and washed. In this way, crystalline N-methyl-pipecolic acid-2,6-dimethylanilide is obtained.
Eksempel 4. Example 4.
10 vektdeler pipekolinsyre-2,6-dimetyl-anilid fremstillet som angitt i eksempel 2 oppløses i 60 deler toluol. Oppløsningen tilsettes 6,4 deler cyklopentylbromid og 5 deler kaliumkarbonat. Etter 10 timers opp-varmning under tilbakeløpskjøling med stadig omrøring filtreres oppløsningen, og filtratet inndampes til tørrhet. Residuet oppløses i fortynnet saltsyre, behandles med trekull og felles med alkali. Herved får man krystallinsk N-cyklopentyl-pipeko-linsyre-2,6-dimetylanilid. 10 parts by weight of pipecolic acid-2,6-dimethylanilide prepared as indicated in example 2 are dissolved in 60 parts of toluene. 6.4 parts of cyclopentyl bromide and 5 parts of potassium carbonate are added to the solution. After 10 hours of heating under reflux with constant stirring, the solution is filtered, and the filtrate is evaporated to dryness. The residue is dissolved in dilute hydrochloric acid, treated with charcoal and precipitated with alkali. This gives crystalline N-cyclopentyl-pipecolic acid-2,6-dimethylanilide.
Eksempel 5. Example 5.
184 vektdeler pipekolinsyreklorid-hydroklorid bringes på en måte tilsvaren-de den i eksempel 1 beskrevne til å reagere med 579 deler 2,6-dimetyl-4-normalt-butoksyanilin. Man får pipekolinsyre-2,6-dimejtyl-4-normalt-butoksyanilid. 10 deler av denne forbindelse oppløses i 20 volumdeler metylalkohol. Til den erholdte opp-løsning tilsettes 4,2 vektdeler dimetylsulfat og 4 deler kaliumkarbonat. Blandingen oppvarmes under tilbakeløpskjøling og oppvarmes i 10 timer, avkjøles, filtreres og inndampes til tørrhet. Residuet opp-løses i fortynnet saltsyre, behandles med trekull og felles påny med alkali, hvorved man får N-metyl-pipekolinsyre-2,6-dimetyl-4-normalt-butoksyanilid. 184 parts by weight of pipecolic acid chloride hydrochloride are brought to react with 579 parts of 2,6-dimethyl-4-normal-butoxyaniline in a manner corresponding to that described in example 1. Pipecolic acid-2,6-dimethyl-4-normal-butoxyanilide is obtained. 10 parts of this compound are dissolved in 20 parts by volume of methyl alcohol. To the solution obtained, 4.2 parts by weight of dimethyl sulphate and 4 parts of potassium carbonate are added. The mixture is heated under reflux and heated for 10 hours, cooled, filtered and evaporated to dryness. The residue is dissolved in dilute hydrochloric acid, treated with charcoal and combined again with alkali, whereby N-methyl-pipecolic acid-2,6-dimethyl-4-normal-butoxyanilide is obtained.
Eksempel 6. Example 6.
184 vektdeler nipekotinsyreklorid-hydroklorid bringes på en måte tilsvaren-. de den i eksempel 1 beskrevne til å reagere med 263 deler 2-etyl-anilin, hvorved man får nipekotinsyre-2-etylanilid. 10 deler av denne forbindelse oppløses i 20 volumdeler isopropylalkohol. Til den erholdte oppløs-ning tilsettes 5,3 vektdeler isopropylbromid 184 parts by weight of nipecotinic acid chloride-hydrochloride is in a way brought to the equivalent. those described in example 1 to react with 263 parts of 2-ethylaniline, whereby nipecotic acid-2-ethylanilide is obtained. 10 parts of this compound are dissolved in 20 parts by volume of isopropyl alcohol. 5.3 parts by weight of isopropyl bromide are added to the solution obtained
og 5 deler kaliumkarbonat. Blandingen oppvarmes under tilbakeløpskjøling og om-røring i 12 timer, filtreres og inndampes til tørrhet. Etter oppløsning av residuet i fortynnet saltsyre og utfelning påny med alkali fåes N-isopropyl-nipekotinsyre-2-etylanilid i form av den frie base. and 5 parts potassium carbonate. The mixture is heated under reflux and stirring for 12 hours, filtered and evaporated to dryness. After dissolving the residue in dilute hydrochloric acid and precipitation again with alkali, N-isopropyl-nipecotic acid-2-ethylanilide is obtained in the form of the free base.
Eksempel 7. Example 7.
184 vektdeler av nipekotinsyreklorid-hydroklorid bringes på en måte tilsvaren-de den i eksempel 1 beskrevne til å reagere med 2,6-dimetyl-4-hydroksyanilid. Man får nipekotinsyre-2,6-dimetyl-4-hydr-oksyanilid. 10 deler av denne forbindelse oppløses i 60 deler toluol og 6,6 deler cyklo-heksylbromid, og den erholdte oppløsning tilsettes 5 deler kaliumkarbonat. Etter opp-varmning under tilbakeløpskjøling og om-røring i 10 timer nedkjøles oppløsningen, filtreres og inndampes. Residuet oppløses i fortynnet saltsyre, behandles med trekull og felles påny med alkali. Man får krystallinsk N-cykloheksyl-nipekotinsyre-2,6-dimetyl-4-hydroksyanilid. 184 parts by weight of nipecotic acid chloride-hydrochloride are brought to react with 2,6-dimethyl-4-hydroxyanilide in a manner corresponding to that described in example 1. Nipecotic acid-2,6-dimethyl-4-hydroxyanilide is obtained. 10 parts of this compound are dissolved in 60 parts of toluene and 6.6 parts of cyclohexyl bromide, and 5 parts of potassium carbonate are added to the resulting solution. After heating under reflux and stirring for 10 hours, the solution is cooled, filtered and evaporated. The residue is dissolved in dilute hydrochloric acid, treated with charcoal and combined again with alkali. Crystalline N-cyclohexyl-nipecotic acid-2,6-dimethyl-4-hydroxyanilide is obtained.
Eksempel 8. Example 8.
184 vektdeler av isonipekotinsyreklorid-hydroklorid bringes på en måte tilsvaren-de den i eksempel 1 beskrevne til å reagere med 279 deler anilin, hvorved man får isonipekotinsyreanilid. 10 deler av denne forbindelse oppløses i 20 volumdeler metanol, og til den erholdte oppløsning tilsettes 6,2 vektdeler dimetylsulfat og 5,5 deler kaliumkarbonat. Blandingen oppvarmes under tilbakeløpskjøling og omrøring i 10 timer, nedkjøles, filtreres og inndampes. Etter oppløsning av residuet i fortynnet saltsyre, behandling av oppløsningen med trekull og felning påny med alkali får man 184 parts by weight of isonipecotinic acid chloride-hydrochloride are brought to react with 279 parts of aniline in a manner corresponding to that described in example 1, whereby isonipecotinic acid anilide is obtained. 10 parts of this compound are dissolved in 20 parts by volume of methanol, and 6.2 parts by weight of dimethyl sulphate and 5.5 parts of potassium carbonate are added to the resulting solution. The mixture is heated under reflux and stirring for 10 hours, cooled, filtered and evaporated. After dissolution of the residue in dilute hydrochloric acid, treatment of the solution with charcoal and precipitation again with alkali, one obtains
N-metylisonipekotinsyreanilid i krystallinsk form. N-methylisonipecotin anilide in crystalline form.
Claims (1)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IT654664 | 1964-03-24 |
Publications (1)
Publication Number | Publication Date |
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NO117868B true NO117868B (en) | 1969-10-06 |
Family
ID=11121186
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO15715365A NO117868B (en) | 1964-03-24 | 1965-03-10 |
Country Status (8)
Country | Link |
---|---|
AT (1) | AT265376B (en) |
BE (1) | BE661547A (en) |
CH (1) | CH427922A (en) |
DE (1) | DE1267288B (en) |
FR (1) | FR1438322A (en) |
GB (1) | GB1078483A (en) |
NL (1) | NL148211B (en) |
NO (1) | NO117868B (en) |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE604025C (en) * | 1931-11-14 | 1934-10-13 | Standard Elek Zitaets Ges A G | Circuit arrangement for telecommunications, especially telephone systems with two-way traffic |
DE1072656B (en) * | 1957-09-26 | 1960-01-07 | Western Electric Company Incorporated New York, N Y (V St A) | , and Carl Brandt Henry Feldman Belleair Clearwater, Fla. (V St A) I Time Division Multiplexed Telephone System |
-
1965
- 1965-02-19 CH CH236165A patent/CH427922A/en unknown
- 1965-03-02 NL NL6502645A patent/NL148211B/en unknown
- 1965-03-03 FR FR7757A patent/FR1438322A/en not_active Expired
- 1965-03-10 NO NO15715365A patent/NO117868B/no unknown
- 1965-03-18 AT AT246665A patent/AT265376B/en active
- 1965-03-19 DE DE19651267288 patent/DE1267288B/en not_active Withdrawn
- 1965-03-23 GB GB1217865A patent/GB1078483A/en not_active Expired
- 1965-03-24 BE BE661547D patent/BE661547A/xx unknown
Also Published As
Publication number | Publication date |
---|---|
CH427922A (en) | 1967-01-15 |
GB1078483A (en) | 1967-08-09 |
NL148211B (en) | 1975-12-15 |
FR1438322A (en) | 1966-05-13 |
AT265376B (en) | 1968-10-10 |
BE661547A (en) | 1965-07-16 |
NL6502645A (en) | 1965-09-27 |
DE1267288B (en) | 1968-05-02 |
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