NO752191L - - Google Patents

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Publication number
NO752191L
NO752191L NO752191A NO752191A NO752191L NO 752191 L NO752191 L NO 752191L NO 752191 A NO752191 A NO 752191A NO 752191 A NO752191 A NO 752191A NO 752191 L NO752191 L NO 752191L
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NO
Norway
Prior art keywords
stated
procedure
stand
hydrogen atom
carbon atoms
Prior art date
Application number
NO752191A
Other languages
Norwegian (no)
Inventor
H Najer
Y R A Pascal
R Dupont
D P R L Giudicelli
Original Assignee
Synthelabo
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Publication date
Application filed by Synthelabo filed Critical Synthelabo
Publication of NO752191L publication Critical patent/NO752191L/no

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D461/00Heterocyclic compounds containing indolo [3,2,1-d,e] pyrido [3,2,1,j] [1,5]-naphthyridine ring systems, e.g. vincamine

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Catalysts (AREA)
  • Solid-Sorbent Or Filter-Aiding Compositions (AREA)
  • Emulsifying, Dispersing, Foam-Producing Or Wetting Agents (AREA)

Abstract

Fremgangsmåte for fremstilling 2-hydroksya1kylde soksyvinkaminater.Process for the preparation of 2-hydroxyalkyl-cold soxyvin kaminates.

Description

Foreliggende oppfinnelse vedrorer en fremgangsmåte forThe present invention relates to a method for

fremstilling a<y>2 hydrosy-alkyldesoksyvinkaminater.preparation of a<y>2 hydroxy-alkyldeoxyvincaminates.

I patent nr. (patentansokning 75.0294) er det beskrevetIt is described in patent no. (patent application 75.0294).

estere av 16,17 dihydroappovinkaminsyre (eller desoksyvinkamin-esters of 16,17 dihydroappovincamine acid (or desoxyvincamine-

syre) tilsvarende den folgende formel:acid) corresponding to the following formula:

hvori R står for et mettet eller umettet alifatisk hydrokarbon med rett eller forgrenet kjede, inneholdende 2-6 karbonatomer og som kan bære 1 eller 2<1>substituenter valgt blant gruppen bestående av hydroksyl eller alkoksy med rett eller forgrenet kjede, inneholdende 1-6 karbonatomer, samt deres syreaddisjons- wherein R represents a saturated or unsaturated straight or branched aliphatic hydrocarbon containing 2-6 carbon atoms and which may bear 1 or 2<1>substituents selected from the group consisting of hydroxyl or straight or branched alkoxy containing 1-6 carbon atoms, as well as their acid addition

salter med farmasøytisk tålbare uorganiske eller organiske syrer.salts with pharmaceutically acceptable inorganic or organic acids.

Disse estere fremstilles ved anvendelse av kjente metoder ogThese esters are produced using known methods and

spesielt etter det folgende reaksjonsskjema:especially according to the following reaction scheme:

I formelen (B) står X for hydroksyl eller et halogenatom In formula (B), X stands for hydroxyl or a halogen atom

og R^og R^- representerer:and R^ and R^- represent:

- hver et hydrogenatom .( i dette tilfelle er (B) de hydroappo-vinkaminsyre eller et av dens halogenider )., - eller de representerer samlet en ytterligere binding ( i dette tilfellet er (B) appovinkaminsyre eller et av dens halogenider - each a hydrogen atom .( in this case (B) they are hydroappovincamic acid or one of its halides)., - or they collectively represent an additional bond ( in this case (B) is appovincamic acid or one of its halides

I formelen (C) har R den samme betydning som i formel (A) og M representerer et hydrogenatom eller et alkalimetalLatom. In formula (C), R has the same meaning as in formula (A) and M represents a hydrogen atom or an alkali metal atom.

Når R-j^ og R2hver representerer et hydrogenatom oppnås ■ forbindelsen med formel (A) direkte og i det tilfelle hvor de samlet står for en ytterligere binding medforer fremgangsmåten et siste trinn med When R-j^ and R2 each represent a hydrogen atom, ■ the compound of formula (A) is obtained directly and in the case where they together represent a further bond, the method entails a final step with

en reduksjon av dobbeltbindingen for oppnåelse av forbindelsen (A). a reduction of the double bond to obtain compound (A).

Man kan likeledes reagere et alkalimetallsalt av desoksyvinkaminsyre med en forbindelse XR (X = halogen). One can likewise react an alkali metal salt of deoxyvinicamic acid with a compound XR (X = halogen).

Den foreliggende oppfinnelse vedrorer en ny fremgangsmåte for fremstilling av 2-hydroksy-alkylestere av desoksyvinkaminsure med den generelle formel (I): The present invention relates to a new process for the production of 2-hydroxy alkyl esters of desoxyvinic acid with the general formula (I):

. hvori R^står for lavere alkyl inneholdende 1-4 karbonatomer . in which R^ stands for lower alkyl containing 1-4 carbon atoms

R2og R^står uavhengig av hverandre for et hydrogenatom eller en me tylgruppe. R 2 and R 4 stand independently of each other for a hydrogen atom or a methyl group.

Det særegne ved fremgangsmåten i henhold til oppfinnelsen er at forbindelser med den generelle formel II: The peculiarity of the method according to the invention is that compounds with the general formula II:

hvori R.^ R2 og R^har samme betydning som i den generelle formel I, in which R.sub.2, R.sub.2 and R.sub.2 have the same meaning as in the general formula I,

R^og R^står enten hver for et hydrogenatom eller samlet forR^ and R^ either each stand for a hydrogen atom or together stand for

en ytterligere binding mellom de to karbonatomer som bærer dem hydrogener i sk, kjemisk eller f'katalytisk-. a further bond between the two carbon atoms that carry them hydrogens in sk, chemically or f'catalytic-.

Den kjemiske hydrogenring gjennomfores ved hjelp av ét alkali-hydrid, foretrukket kaliumborhydrid, under omroring i lopet av minst 12 timer i en alkohol som metanol. The chemical hydrogen ring is carried out by means of an alkali hydride, preferably potassium borohydride, with stirring for at least 12 hours in an alcohol such as methanol.

Den katalytiske hydrogenering gjennomfores fortrinnsvis ved hjelp av rodium på aluminiumoksyd, under et trykk på fra 50..:-- 100 kg/cm<2>og en temperatur på fra 80-150°C, i en alkohol som etanol. The catalytic hydrogenation is preferably carried out using rhodium on aluminum oxide, under a pressure of from 50..:-- 100 kg/cm<2> and a temperature of from 80-150°C, in an alcohol such as ethanol.

Fordelen ved den nye metode i henhold til oppfinnelsen liggerThe advantage of the new method according to the invention lies

i de gode utbytter, og den enkle utforelse.in the good yields, and the simple implementation.

Forbindelsene med den generelle formel II er tidligere kjentThe compounds of the general formula II are previously known

og kan fremstilles ved vanlig forestring ved at man omsetter desoksyvinkamiri-syre eller appovinkaminsyre eller et av deres funksjonelle derivater med et ketonderivat tilsvarende formel III: and can be produced by ordinary esterification by reacting desoxyvincamic acid or appovincamic acid or one of their functional derivatives with a ketone derivative corresponding to formula III:

hvori R^, R 2 og R^ har samme betydning som i formelene I og II og X står for en OH-gruppe eller et halogenatom, foretrukket klor. in which R^, R 2 and R^ have the same meaning as in formulas I and II and X stands for an OH group or a halogen atom, preferably chlorine.

Denne reaksjonen gjennomfores foretrukket ved en temperatur på 75-120°C i et ikke-polart løsningsmiddel, som en eter, et hydrokarbon, et klorert hydrokarbon, dimetylformamid etc. This reaction is preferably carried out at a temperature of 75-120°C in a non-polar solvent, such as an ether, a hydrocarbon, a chlorinated hydrocarbon, dimethylformamide, etc.

Det folgende eksempel illustrerer fremgangsmåten i henhold til oppfinnelsen. The following example illustrates the method according to the invention.

EKSEMPEL:EXAMPLE:

Fremstilling av 2-hydroksy-propyldesoksyvinkaminat a - fra 2-propanondesoksyvinkaminat Preparation of 2-hydroxy-propyldesoxyvincaminate a - from 2-propanedesoxyvincaminate

Til en losning av 11 gram (0,02 mol) 2-propanondesoksyvinkaminat To a solution of 11 grams (0.02 mole) of 2-propane deoxyvincaminate

i 100 ml metanol avkjolt til 0°C tilsettes litt etter litt under omroring 3 gram kaliumborhydrid. Omrøringen av reaksjonsblandingen fortsettes over natten, omtrent 3/4 av løsningsmiddelet avdampes og 150 ml vann tilsettes. Blandingen ekstreheres med etylasitat, torres over natriumsulfat og inndampes til torrhet. Det oppnås 5 gram (utbyttet = 45%) av 2-hydroksypropyldesoksyvinkaminat i form av en kromatografisk ren harpiks. 3 grams of potassium borohydride are added little by little while stirring to 100 ml of methanol cooled to 0°C. Stirring of the reaction mixture is continued overnight, approximately 3/4 of the solvent is evaporated and 150 ml of water is added. The mixture is extracted with ethyl acetate, dried over sodium sulphate and evaporated to dryness. 5 grams (yield = 45%) of 2-hydroxypropyldesoxyvincaminate are obtained in the form of a chromatographically pure resin.

b - fra 2-propanonappovinkaminatb - from 2-propanone appovincamine

I en 250 ml autoklav innfores en opplosning av 15 gram (0,0397 mol) 2-propanonappovinkaminat i 150 ml absolutt etanol og 1 gram 5% In a 250 ml autoclave, introduce a solution of 15 grams (0.0397 mol) of 2-propanone appovincamine in 150 ml of absolute ethanol and 1 gram of 5%

Rh på aluminiumoksyd.Rh on aluminum oxide.

Hydrogeneringen gjennomfores under 90 kg/cm trykk ved 80 C i - ■ lopet av 15 timer. Den oppnådde opplosning filtreres og inndampes til torrhet. Det oppnås 12 gram ( utbyttet = 80% ) 2-hydroksypropyldesoksyvinkaminat i form av en harpiks. The hydrogenation is carried out under 90 kg/cm pressure at 80 C over the course of 15 hours. The solution obtained is filtered and evaporated to dryness. 12 grams (yield = 80%) of 2-hydroxypropyldesoxyvincaminate are obtained in the form of a resin.

Claims (5)

1. Fremgangsmåte for fremstilling av 2-hydroksyalkylestere av desoksyvinkaminsyre med generall' formel I1. Process for the production of 2-hydroxyalkyl esters of deoxyvinicamic acid with general formula I hvori står for lavere alkyl inneholdende 1-4 karbonatomer R2 og R^ står uavhengig av hverandre for et hydrogenatom eller en metylgruppe, karakterisert ved at en forbindelse med den generelle formel II in which stands for lower alkyl containing 1-4 carbon atoms R2 and R^ stand independently of each other for a hydrogen atom or a methyl group, characterized in that a connection with it general formula II - hvori R^ , R2 og R^ har den ovennevnte betydning R^ og R,, står hver for et hydrogenatom eller står samlet for en ytterligere binding mellom de to karbonatomer som bærer dem hydrogeneres kjemisk eller katalytisk. - in which R^ , R 2 and R^ have the above meaning R^ and R,, each stand for a hydrogen atom or collectively stand for a further bond between the two carbon atoms which carry them hydrogenated chemically or catalytically. 2. Fremgangsmåte som angitt i krav 1, karakterisert ved at den kjemiske hydrogenering gjennomfores ved hjelp av et al ka li metallhydrid i alkohol. 2. Procedure as stated in claim 1, characterized in that the chemical hydrogenation is carried out using an alkali metal hydride in alcohol. 3. Fremgangsmåte som angitt i krav 2, karakterisert ved . at det som al kal ime tal Thydr i d anvendes kaliumborhydrid og at det som løsningsmiddel anvendes metanol. 3. Procedure as stated in claim 2, characterized by . that potassium borohydride is used as the alkali metal Thydr i d and that methanol is used as the solvent. 4. Fremgangsmåte som angitt i krav 1, karakterisert ved at den katalytiske hydrogenering gjennomfores under et trykk på fra 50-100 kg/cm og ved en temperatur på 80-150°C i en alkohol. 4. Procedure as stated in claim 1, characterized in that the catalytic hydrogenation is carried out under a pressure of from 50-100 kg/cm and at a temperature of 80-150°C in an alcohol. 5. Fremgangsmåte som angitt i krav 4, karakterisert ved at det som katalysator anvendes 5% rodium på aluminiumoksyd og at det som løsningsmiddel anvendes etanol.5. Procedure as stated in claim 4, characterized in that 5% rhodium on aluminum oxide is used as a catalyst and that ethanol is used as a solvent.
NO752191A 1974-06-21 1975-06-19 NO752191L (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
FR7421582A FR2275455A1 (en) 1974-06-21 1974-06-21 D-Hydroxyalkyl desoxyvincaminates - by hydrogenation of 2-oxoalkyl desoxyvincaminates and the corresp. apovincaminates (NO190176)

Publications (1)

Publication Number Publication Date
NO752191L true NO752191L (en) 1975-12-23

Family

ID=9140348

Family Applications (1)

Application Number Title Priority Date Filing Date
NO752191A NO752191L (en) 1974-06-21 1975-06-19

Country Status (9)

Country Link
JP (1) JPS532880B2 (en)
DK (1) DK280175A (en)
ES (1) ES438736A1 (en)
FI (1) FI751820A7 (en)
FR (1) FR2275455A1 (en)
HU (1) HU169622B (en)
LU (1) LU72780A1 (en)
NO (1) NO752191L (en)
SE (1) SE7506949L (en)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5413194U (en) * 1977-06-29 1979-01-27
DE2952939C2 (en) * 1978-07-11 1986-01-09 Molins Ltd., London Packing machine for cigarettes
JP2669250B2 (en) * 1992-02-24 1997-10-27 東洋製罐株式会社 Method and apparatus for collecting and supplying cylindrical cans
CN114249721B (en) * 2021-11-29 2023-10-17 南京中医药大学 Application of vincamine PEG derivative in preparing medicament for treating diabetic peripheral neuropathy, diabetic foot and pulmonary fibrosis
CN114920743B (en) * 2022-05-09 2023-08-04 南京中医药大学 Indole alkaloid and preparation method and application thereof

Also Published As

Publication number Publication date
JPS5141398A (en) 1976-04-07
ES438736A1 (en) 1977-03-16
FR2275455A1 (en) 1976-01-16
SE7506949L (en) 1975-12-22
FI751820A7 (en) 1975-12-22
FR2275455B1 (en) 1976-10-22
DK280175A (en) 1975-12-22
JPS532880B2 (en) 1978-02-01
LU72780A1 (en) 1976-11-11
HU169622B (en) 1976-12-28

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