NO126937B - - Google Patents
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- NO126937B NO126937B NO45769A NO45769A NO126937B NO 126937 B NO126937 B NO 126937B NO 45769 A NO45769 A NO 45769A NO 45769 A NO45769 A NO 45769A NO 126937 B NO126937 B NO 126937B
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- Norway
- Prior art keywords
- piperidyl
- phenyl
- threo
- methanol
- melting point
- Prior art date
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- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 69
- 238000000034 method Methods 0.000 claims description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims description 8
- 230000010933 acylation Effects 0.000 claims description 5
- 238000005917 acylation reaction Methods 0.000 claims description 5
- 150000001408 amides Chemical class 0.000 claims description 5
- 150000002148 esters Chemical class 0.000 claims description 5
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 238000006386 neutralization reaction Methods 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 3
- HFFLGKNGCAIQMO-UHFFFAOYSA-N trichloroacetaldehyde Chemical compound ClC(Cl)(Cl)C=O HFFLGKNGCAIQMO-UHFFFAOYSA-N 0.000 claims description 3
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims description 2
- 239000003513 alkali Substances 0.000 claims description 2
- 150000001342 alkaline earth metals Chemical class 0.000 claims description 2
- 150000008064 anhydrides Chemical class 0.000 claims description 2
- 230000005012 migration Effects 0.000 claims description 2
- 238000013508 migration Methods 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 150000007530 organic bases Chemical class 0.000 claims description 2
- 239000003960 organic solvent Substances 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 1
- 230000004048 modification Effects 0.000 claims 1
- 238000012986 modification Methods 0.000 claims 1
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 1
- 125000004430 oxygen atom Chemical group O* 0.000 claims 1
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 22
- 238000002844 melting Methods 0.000 description 17
- 230000008018 melting Effects 0.000 description 17
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 12
- 239000000243 solution Substances 0.000 description 11
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- FBBDOOHMGLLEGJ-UHFFFAOYSA-N methane;hydrochloride Chemical compound C.Cl FBBDOOHMGLLEGJ-UHFFFAOYSA-N 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- NJQFUWRRXYGPLE-UHFFFAOYSA-N 1-[2-[hydroxy(phenyl)methyl]piperidin-1-yl]ethanone Chemical compound C(C)(=O)N1C(CCCC1)C(O)C1=CC=CC=C1 NJQFUWRRXYGPLE-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 150000001414 amino alcohols Chemical class 0.000 description 1
- 229940125681 anticonvulsant agent Drugs 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000010908 decantation Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000008240 homogeneous mixture Substances 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- FUKUFMFMCZIRNT-UHFFFAOYSA-N hydron;methanol;chloride Chemical compound Cl.OC FUKUFMFMCZIRNT-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 239000003326 hypnotic agent Substances 0.000 description 1
- 230000000147 hypnotic effect Effects 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 150000003053 piperidines Chemical class 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 229940125723 sedative agent Drugs 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
Classifications
-
- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01B—CABLES; CONDUCTORS; INSULATORS; SELECTION OF MATERIALS FOR THEIR CONDUCTIVE, INSULATING OR DIELECTRIC PROPERTIES
- H01B1/00—Conductors or conductive bodies characterised by the conductive materials; Selection of materials as conductors
- H01B1/02—Conductors or conductive bodies characterised by the conductive materials; Selection of materials as conductors mainly consisting of metals or alloys
- H01B1/023—Alloys based on aluminium
-
- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01B—CABLES; CONDUCTORS; INSULATORS; SELECTION OF MATERIALS FOR THEIR CONDUCTIVE, INSULATING OR DIELECTRIC PROPERTIES
- H01B5/00—Non-insulated conductors or conductive bodies characterised by their form
- H01B5/08—Several wires or the like stranded in the form of a rope
- H01B5/10—Several wires or the like stranded in the form of a rope stranded around a space, insulating material, or dissimilar conducting material
- H01B5/102—Several wires or the like stranded in the form of a rope stranded around a space, insulating material, or dissimilar conducting material stranded around a high tensile strength core
- H01B5/104—Several wires or the like stranded in the form of a rope stranded around a space, insulating material, or dissimilar conducting material stranded around a high tensile strength core composed of metallic wires, e.g. steel wires
Landscapes
- Non-Insulated Conductors (AREA)
- Conductive Materials (AREA)
- Hydrogenated Pyridines (AREA)
Description
Fremgangsmåte for fremstilling av amider av treo-l-fenyl-l-(2-piperidyl)-metanol. Process for the preparation of amides of threo-1-phenyl-1-(2-piperidyl)-methanol.
Nærværende oppfinnelse angår en The present invention relates to a
fremgangsmåte for fremstilling av piperidinderivater. method for the preparation of piperidine derivatives.
Derivatene etter oppfinnelsen tilsvarer The derivatives according to the invention correspond
den følgende generelle formel: the following general formula:
i hvilken R betyr et hydrogenatom eller en alkylgruppe, f. eks. en lavere alkylgruppe som inneholder 1 til 4 kullstoffatomer. Disse derivater har to asymmetriske kullstoffatomer og kan derfor eksistere som et racemat i erytro og treo stereoisomeriske former tilsvarende erytro- og treoformene av l-fenyl-l-(2-piperidyl)metanol med formelen: og disse to former har de følgende karak-teristika: in which R means a hydrogen atom or an alkyl group, e.g. a lower alkyl group containing 1 to 4 carbon atoms. These derivatives have two asymmetric carbon atoms and can therefore exist as a racemate in erythro and threo stereoisomeric forms corresponding to the erythro and threo forms of l-phenyl-l-(2-piperidyl)methanol with the formula: and these two forms have the following characteristics :
Nærværende oppfinnelse vedrører bare The present invention relates only to
racemiske og optisk aktive treo-derivater. racemic and optically active threo derivs.
I følge nærværende oppfinnelse kan According to the present invention,
forannevnte treo-piperidinderivater frem-stilles ved de følgende metoder under bruk aforementioned threo-piperidine derivatives are produced by the following methods in use
av racemiske blandinger eller optisk aktive of racemic mixtures or optically active
isomerer av de angitte utgangsmaterialer. isomers of the indicated starting materials.
(1) Kontrollert acylering av treo-1-fenyl-l-(2-piperidyl)metanol etter kjente (1) Controlled acylation of threo-1-phenyl-1-(2-piperidyl)methanol according to known methods
metoder for omdannelsen av aminoalkoho-ler til de tilsvarende amider. Acyleringen methods for the conversion of amino alcohols to the corresponding amides. The acylation
foretas fortrinnsvis ved innvirkning av et is preferably carried out by the impact of a
syreklorid, en ester eller et anhydrid av en acid chloride, an ester or an anhydride of one
syre RCOOH, hvor R er som foran definert. I det tilfelle hvor R betyr et hydrogenatom kan formamid eller kloral brukes. acid RCOOH, where R is as defined above. In the case where R represents a hydrogen atom, formamide or chloral can be used.
Ved uttrykket «kjente metoder, slik som brukt i den foreliggende fremstilling og ved etterfølgende påstander, forstås metoder hittil brukt eller beskrevet i den kjemiske litteratur. The expression "known methods, such as used in the present presentation and in subsequent claims, means methods hitherto used or described in the chemical literature.
(2) Nøytralisering eller alkalisering av en oppløsning av et salt av en ester av treo- 1-f enyl-1 - (2-piperidyl) metanol med formelen: (2) Neutralization or alkalization of a solution of a salt of an ester of threo-1-phenyl-1-(2-piperidyl)methanol of the formula:
hvor R er som foran definert, i vann eller et organisk oppløsningsmiddel. Frigjørin-gen av basen følges av vandring av -COR-gruppen fra oksygenet til nitrogenet. where R is as defined above, in water or an organic solvent. The release of the base is followed by migration of the -COR group from the oxygen to the nitrogen.
Nøy tralisasj onen eller alkaliseringen kan utføres ved hjelp av et alkali- eller jordalkalimetallderivat som hydroksyd,kar-bonat, bikarbonat eller alkoholat eller en organisk base som f. eks. trietylamin. The neutralization or alkalization can be carried out with the help of an alkali or alkaline earth metal derivative such as hydroxide, carbonate, bicarbonate or alcoholate or an organic base such as e.g. triethylamine.
Treo-1 -f enyl- (2-piperidyl) metanol og estrene brukt som utgangsmaterialer ved forannevnte metoder (1) og (2) kan frem-stilles som angitt i patent nr. 96 447. Treo-1-phenyl-(2-piperidyl) methanol and the esters used as starting materials in the aforementioned methods (1) and (2) can be produced as indicated in patent no. 96 447.
Derivatene etter nærværende oppfinnelse er i besiddelse av verdifulle farma-kodynamiske egenskaper og er spesielt an-vendelige som sedativer, hypnotika og anti-krampemidler. Disse sedative egenskaper er helt uventet da de tilsvarende O-acy-lerte isomerer i motsetning hertil er i besiddelse av stimulerende aktivitet. Av størst interesse er forbindelsene av formelen I, hvor R er et lavere alkyl, spesielt en metyl-gruppe. The derivatives according to the present invention possess valuable pharmacodynamic properties and are particularly useful as sedatives, hypnotics and anticonvulsants. These sedative properties are completely unexpected as the corresponding O-acylated isomers, in contrast, possess stimulating activity. Of greatest interest are the compounds of formula I, where R is a lower alkyl, especially a methyl group.
De følgende eksempler illustrerer oppfinnelsen. The following examples illustrate the invention.
Eksempel 1: Example 1:
En suspensjon av treo-l-fenyl-l-(2-piperidyl)metanol (30 g), smeltepunkt 177° C, i formamid oppvarmes i 3 timer ved 150° C. En homogen blanding danner seg. Over-skuddet av formamid fordampes under re-dusert trykk (2 mm kvikksølv) og residuet tas opp i benzol (130 cm<3>). Produktet av-farges med trekull, og petroleter (70 cm<3>) tilsettes. Amidet (32,3 g) utvinnes og kry-stalliseres fra metyl-etyl-keton. Racemisk treo-1 -f enyl-1 - (1 -f ormyl-2-piperidyl) - metanol oppnås i form av fargeløse nåler, smeltepunkt 131° C (cap.). A suspension of threo-1-phenyl-1-(2-piperidyl)methanol (30 g), melting point 177° C., in formamide is heated for 3 hours at 150° C. A homogeneous mixture forms. The excess of formamide is evaporated under reduced pressure (2 mm of mercury) and the residue is taken up in benzene (130 cm<3>). The product is de-coloured with charcoal, and petroleum ether (70 cm<3>) is added. The amide (32.3 g) is recovered and crystallized from methyl ethyl ketone. Racemic threo-1-phenyl-1-(1-formyl-2-piperidyl)-methanol is obtained in the form of colorless needles, melting point 131° C (cap.).
Eksempel 2: Treo-1 -f enyl-1 - (2-piperidyl) metanol (1 g), smeltepunkt 177—178° C, tilsettes med omrøring til acetanhydrid (2 cm<3>). Example 2: Treo-1-phenyl-1-(2-piperidyl) methanol (1 g), melting point 177-178° C, is added with stirring to acetic anhydride (2 cm<3>).
Reaksjonen er eksotermisk, og blan-dingen blir homogen i løpet av 2 minutter. Etter 10 minutter tilsettes destillert vann (13 cm<3>). Natriumbikarbonat (4,5 g) tilsettes derpå i små porsjoner. Reaksjonsblandingen (pH 7) holdes ved en temperatur under 15° C og omrøres kontinuerlig. Den tillates derpå å henstå i 1 time og ek-straheres med kloroform. Kloroformoppløs-ningen tørkes over natriumsulfat og fordampes. Den tilbakeblivende resterende olje tas opp i kokende benzol (5 cm<3>), og petroleter (80 cm3) tilsettes. Racemisk treo-1 -f enyl-1- (-acetyl-2-piperidyl) metanol (0,39 g) oppnås, smeltepunkt ca. 146— 147° C. (Kofler) etter rensing. The reaction is exothermic, and the mixture becomes homogeneous within 2 minutes. After 10 minutes, distilled water (13 cm<3>) is added. Sodium bicarbonate (4.5 g) is then added in small portions. The reaction mixture (pH 7) is kept at a temperature below 15° C and stirred continuously. It is then allowed to stand for 1 hour and extracted with chloroform. The chloroform solution is dried over sodium sulphate and evaporated. The remaining residual oil is taken up in boiling benzene (5 cm3), and petroleum ether (80 cm3) is added. Racemic threo-1-phenyl-1-(-acetyl-2-piperidyl)methanol (0.39 g) is obtained, melting point ca. 146— 147° C. (Kofler) after purification.
Eksempel 3: Example 3:
Kloral (14,7 g) tilsettes gradvis med omrøring til en suspensjon av treo-1-f enyl - l-(2-piperidyl)metanol (19,1 g) i kloroform (100 cm<3>). Omrøringen fortsettes i 5 timer ved 20° C, og reaksjonen fullendes ved oppvarmning i 1 time på vannbad. Kloroform-oppløsningen avkjøles og vaskes med nor-mal klorvannstoffsyre (2 x 50 cm<3>). Etter tørking over natriumsulfat og fordampning av kloroformen oppnås et oljelignende re-siduum som behandles med metyl-etyl-keton (20 cm<3>). Racemisk treo-l-fenyl-1-(l-formyl-2-piperidyl) metanol (13,8 g), smeltepunkt 128—131° C (Kofler), bunn-felles. Det smelter ved 133° C etter om-krystallisasjon fra metyl-etyl-keton. Chloral (14.7 g) is gradually added with stirring to a suspension of threo-1-phenyl-1-(2-piperidyl)methanol (19.1 g) in chloroform (100 cm<3>). Stirring is continued for 5 hours at 20° C, and the reaction is completed by heating for 1 hour in a water bath. The chloroform solution is cooled and washed with normal hydrochloric acid (2 x 50 cm<3>). After drying over sodium sulphate and evaporation of the chloroform, an oil-like residue is obtained which is treated with methyl ethyl ketone (20 cm<3>). Racemic threo-1-phenyl-1-(1-formyl-2-piperidyl)methanol (13.8 g), melting point 128-131° C (Kofler), bottom common. It melts at 133° C after recrystallization from methyl ethyl ketone.
Eksempel 4: Example 4:
En blanding av propionylklorid (160 g) og treo-l-fenyl-l-(2-piperidyl)metanol (13 A mixture of propionyl chloride (160 g) and threo-l-phenyl-l-(2-piperidyl)methanol (13
g) oppvarmes ved 80° C i iy4 time. Etter avkjøling filtreres reaksjonsblandingen, og g) is heated at 80° C. for iy4 hours. After cooling, the reaction mixture is filtered, and
det faste fraskilte produkt vaskes med eter. Det faste produkt oppløses i vann (200 cm<3>), og kaliumkarbonat (20 g) tilsettes i små porsjoner til den oppnådde oppløsning. En olje skiller seg ut som kry-stalliserer hurtig. Det oppnådde rå produkt omkrystalliseres fra metyl-etyl-keton (100 cm<3>) og gir racemisk treo-l-fenyl-l-(l-propionyl-2-piperidyl) metanol (10 g) som foreligger i form av hvite krystaller, smeltepunkt 133—134° C. (Kofler-blokk). the solid separated product is washed with ether. The solid product is dissolved in water (200 cm<3>), and potassium carbonate (20 g) is added in small portions to the solution obtained. An oil stands out which crystallizes quickly. The crude product obtained is recrystallized from methyl ethyl ketone (100 cm<3>) to give racemic threo-l-phenyl-l-(l-propionyl-2-piperidyl)methanol (10 g) which is present in the form of white crystals , melting point 133—134° C. (Kofler block).
Eksempel 5: Treo-l-fenyl-1-(2-piperidyl) metanol-hydroklorid (2,38 g), smeltepunkt 120° C oppløses i destillert vann (15 cm<3>). Det av-kjøles utvendig med is og acetanhydrid (3 cm<3>) tilsettes, fulgt av natriumbikarbonat (8 g) i små porsjoner. Reaksjonsblandingen holdes ved en temperatur under 2° C og omrøres. pH-verdien av oppløsningen reguleres til 7 med eddik-syre. Et hvitt bunnfall danner seg som oppløses igjen ved oppvarmning og omkrystalliseres ved av-kjøling — det er racemisk treo-l-fenyl-1-(l-acetyl-2-piperidyl) metanol (0,6 g), smeltepunkt 146—147° C. (Kofler). Example 5: Threo-1-phenyl-1-(2-piperidyl) methanol hydrochloride (2.38 g), melting point 120° C. is dissolved in distilled water (15 cm<3>). It is cooled externally with ice and acetic anhydride (3 cm<3>) is added, followed by sodium bicarbonate (8 g) in small portions. The reaction mixture is kept at a temperature below 2° C and stirred. The pH value of the solution is adjusted to 7 with acetic acid. A white precipitate forms which redissolves on heating and recrystallizes on cooling — it is racemic threo-l-phenyl-1-(l-acetyl-2-piperidyl)methanol (0.6 g), melting point 146-147° C. (Kofler).
Eksempler 6: Konsentrert natriumhydroksyd (20 cm<3>) tilsettes til en oppløsning av treo-1-acetoksy-l-fenyl-1-(2-piperidyl)-metan-hydroklorid (10 g), smeltepunkt 229—230° C (cap.) i destillert vann (170 cm<3>). Treo-l-fenyl-l-(acetyl-2-piperidyl)metanol skiller seg fra i form av et hvitt bunnfall. Det samles opp, tørkes og omkrystalliseres fra kokende etalacetat (100 cm<3>). Et produkt (6,5 g) oppnås som har smeltepunkt 146— 147° C. (Kofler). Examples 6: Concentrated sodium hydroxide (20 cm<3>) is added to a solution of threo-1-acetoxy-1-phenyl-1-(2-piperidyl)-methane hydrochloride (10 g), melting point 229-230° C ( cap.) in distilled water (170 cm<3>). Threo-l-phenyl-l-(acetyl-2-piperidyl)methanol separates as a white precipitate. It is collected, dried and recrystallized from boiling ethyl acetate (100 cm<3>). A product (6.5 g) is obtained which has a melting point of 146-147° C. (Kofler).
Eksempel 7: Example 7:
Ved å gå frem som i eksempel 6, men ved å gå ut fra venstredreiende treo-1-acetoksy-l-f enyl-1-(2-piperidyl)metan-hydroklorid, smeltepunkt 232° C (cap.) [a] Proceeding as in Example 6, but starting from levorotatory threo-1-acetoxy-1-phenyl-1-(2-piperidyl)methane hydrochloride, melting point 232° C (cap.) [a]
20 20
D = —60° (C = 0,4, kloroform) oppnås venstredreiende treo-l-f enyl-1-(l-acetyl-2-piperidyl) metanol, smeltepunkt 146° C D = —60° (C = 0.4, chloroform) left-rotating threo-1-phenyl-1-(1-acetyl-2-piperidyl) methanol is obtained, melting point 146° C
20 (cap.) [a] D = —86° (C = 0,64, kloroform). 20 (cap.) [a] D = —86° (C = 0.64, chloroform).
Eksempel 8: Example 8:
Ved å gå frem som i eksempel 6, men ved å gå ut fra høyredreiende treo-l-ace-toksy-1 -f enyl- (2-piperidyl) metanhydro-20 klorid, smeltepunkt 232° C (cap.) [a] D Proceeding as in example 6, but starting from dextrorotatory threo-1-ace-toxy-1-phenyl-(2-piperidyl)methanehydrochloride, melting point 232° C (cap.) [a] D
= + 71° (C = 0,3, kloroform) oppnås høy-redreiende 1-f enyl-1- (l-acetyl-2-piperidyl)metanol, smeltepunkt 146° C (cap.), = + 71° (C = 0.3, chloroform) high-reactivity 1-phenyl-1-(1-acetyl-2-piperidyl)methanol is obtained, melting point 146° C (cap.),
D D
[a] 20 = + 100° (C = 0,87, kloroform). [α] 20 = + 100° (C = 0.87, chloroform).
Eksempel 9: Treo-1-acetoksy-1-feny 1-1-(2-piper i-dyl)metanhydroklorid (1 g) oppløses i vann (50 cm<3>) ved oppvarmning. Trietylamin (1 cm<3>) tilsettes og l-fenyl-l-(l-acetyl-2-piperidyl) metanol faller ut. Etter filtrering og tørking oppnås der et produkt (0,67 g), smeltepunkt 146—147° C. (Kofler). Example 9: Threo-1-acetoxy-1-phenyl 1-1-(2-piperidyl)methane hydrochloride (1 g) is dissolved in water (50 cm<3>) by heating. Triethylamine (1 cm<3>) is added and l-phenyl-l-(l-acetyl-2-piperidyl)methanol precipitates out. After filtration and drying, a product is obtained (0.67 g), melting point 146-147° C. (Kofler).
Eksempel 10: Example 10:
En 2,5 % oppløsning av natriumbikar bonat (20 cm<3>) tilsettes gradvis under kraf- A 2.5% solution of sodium beaker bonat (20 cm<3>) is gradually added under force
tig omrøring til en oppløsning av treo-1-acetoksy-l-f enyl-1-(2-piperidyl) metan-klorvannstoff (1,7 g) i vann (30 cm<3>) og kloroform (30 cm<3>). pH-verdien av den vandige oppløsning er 7. Etter hurtig de-kantering vaskes kloroformoppløsningen, tørkes over natriumsulfat og fordampes. Der oppnås racemisk treo-l-f enyl-1-(ace-tyl-2-piperidyl) metanol (0,6 g), smeltepunkt 146° C. (Kofler). tig stirring to a solution of threo-1-acetoxy-1-phenyl-1-(2-piperidyl)methane-hydrogen chloride (1.7 g) in water (30 cm<3>) and chloroform (30 cm<3>). The pH value of the aqueous solution is 7. After rapid decantation, the chloroform solution is washed, dried over sodium sulfate and evaporated. There is obtained racemic threo-1-phenyl-1-(acetyl-2-piperidyl) methanol (0.6 g), melting point 146° C. (Kofler).
Eksempel 11: Example 11:
En 12,7 % oppløsning (1,75 cm<3>) av na-triummetoksyd i metanol tilsettes til en oppløsning av treo-l-acetoksy-l-fenyl-1-(2-piperidyl)metanklorvannstoff (1,1 g) i vannfritt metanol (30 g). Metanolen fordampes, og residuet behandles med kokende etylacetat (100 cm<3>). Produktet som oppnås ved fordampning er racemisk treo-1 -f enyl-1 - (1 -acetyl-2-piperidyl) metanol, smeltepunkt 146—147° C. (Kofler). A 12.7% solution (1.75 cm<3>) of sodium methoxide in methanol is added to a solution of threo-1-acetoxy-1-phenyl-1-(2-piperidyl)methane chlorohydrogen (1.1 g) in anhydrous methanol (30 g). The methanol is evaporated, and the residue is treated with boiling ethyl acetate (100 cm<3>). The product obtained by evaporation is racemic threo-1-phenyl-1-(1-acetyl-2-piperidyl)methanol, melting point 146-147° C. (Kofler).
Claims (5)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB150169A GB1221171A (en) | 1969-01-10 | 1969-01-10 | Improvements in or relating to electric conductor cables for use in overhead power transmissions |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO126937B true NO126937B (en) | 1973-04-09 |
Family
ID=9723097
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO45769A NO126937B (en) | 1969-01-10 | 1969-02-06 |
Country Status (8)
| Country | Link |
|---|---|
| JP (1) | JPS5416030B1 (en) |
| BE (1) | BE728440A (en) |
| CH (1) | CH500565A (en) |
| FR (1) | FR2028061A1 (en) |
| GB (1) | GB1221171A (en) |
| NL (1) | NL6901963A (en) |
| NO (1) | NO126937B (en) |
| SE (1) | SE342108B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5243137A (en) * | 1992-06-25 | 1993-09-07 | Southwire Company | Overhead transmission conductor |
-
1969
- 1969-01-10 GB GB150169A patent/GB1221171A/en not_active Expired
- 1969-02-06 NO NO45769A patent/NO126937B/no unknown
- 1969-02-07 NL NL6901963A patent/NL6901963A/xx unknown
- 1969-02-12 CH CH215469A patent/CH500565A/en not_active IP Right Cessation
- 1969-02-14 FR FR6903651A patent/FR2028061A1/fr not_active Withdrawn
- 1969-02-14 SE SE208969A patent/SE342108B/xx unknown
- 1969-02-14 BE BE728440D patent/BE728440A/xx unknown
- 1969-02-17 JP JP1172069A patent/JPS5416030B1/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| SE342108B (en) | 1972-01-24 |
| BE728440A (en) | 1969-07-16 |
| FR2028061A1 (en) | 1970-10-09 |
| NL6901963A (en) | 1970-07-14 |
| CH500565A (en) | 1970-12-15 |
| JPS5416030B1 (en) | 1979-06-19 |
| GB1221171A (en) | 1971-02-03 |
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