NO833439L - DIASTEROOMER AND PROCEDURE FOR THEIR PREPARATION - Google Patents

DIASTEROOMER AND PROCEDURE FOR THEIR PREPARATION

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Publication number
NO833439L
NO833439L NO833439A NO833439A NO833439L NO 833439 L NO833439 L NO 833439L NO 833439 A NO833439 A NO 833439A NO 833439 A NO833439 A NO 833439A NO 833439 L NO833439 L NO 833439L
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toluoyl
ethyl
aminomethyl
pyrrolidine
tartrate
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NO833439A
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Norwegian (no)
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Catrine Margareta Fredlund
Jan Aake Froborg
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Astra Pharma Prod
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Publication of NO833439L publication Critical patent/NO833439L/en

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D207/00Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom 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
    • C07D207/08Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom 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 radicals, substituted by hetero atoms, attached to ring carbon atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07BGENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B57/00Separation of optically-active compounds
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/76Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Pyrrole Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Steroid Compounds (AREA)

Description

Foreliggende oppfinnelse vedrører nye diastereomerer ogThe present invention relates to new diastereomers and

en ny fremgangsmåte for deres fremstilling.a new method for their production.

Diastereomerene er nyttige som mellomprodukter for fremstilling av farmasøytisk aktive forbindelser. The diastereomers are useful as intermediates for the preparation of pharmaceutically active compounds.

Fra britisk patent nr. 1.207.752 er det kjent at 1-etyl-2-aminometyl-pyrrolidin From British patent no. 1,207,752 it is known that 1-ethyl-2-aminomethyl-pyrrolidine

kan spaltes i sine to optiske isomerer ved hjelp av optisk aktiv vinsyre. D(-)-vinsyre danner et krystallinsk tartrat med det venstredreiende amin mens L(+)-vinsyre danner et krystallinsk tartrat med det høyredreiende amin. Det frie aminet oppnås deretter ved oppløsning av tartratet i vann, mediet gjøres alkalisk, og aminet ekstraheres og destilleres. Metoden har dårlig reproduserbarhet ved utfelling av rå-tartratet og resulterer i lave utbytter (under 40%). P.g.a. at det ikke foretas noen omkrystallisering, men snarere en rekke utlutinger, forårsaker utilfredsstillende renhet i det urene bunnfall meget tidskrevende og tvilsomme rensings-prosesser. Strukturen til krystallene i det urene bunnfall er av en type som gjør reaksjonsblandingen meget tyktflytende og vanskelig å filtrere. Formålet med foreliggende oppfinnelse er å tilveiebringe en fremgangsmåte for spalting av 1-etyl-2-aminometyl-pyrrolidin uten de innebyggede ulemper ved fremgangsmåten hvorved vinsyre anvendes, dvs. dårlig utbytte og optisk renhet, dårlig reproduserbarhet, mangel på omkrystallisering og dårlige krystaller. can be resolved into its two optical isomers using optically active tartaric acid. D(-)-tartaric acid forms a crystalline tartrate with the levorotatory amine while L(+)-tartaric acid forms a crystalline tartrate with the dextrorotatory amine. The free amine is then obtained by dissolving the tartrate in water, the medium is made alkaline, and the amine is extracted and distilled. The method has poor reproducibility when the crude tartrate is precipitated and results in low yields (below 40%). Because of. that no recrystallization is carried out, but rather a series of leachings, causes unsatisfactory purity in the impure precipitate, very time-consuming and questionable purification processes. The structure of the crystals in the impure precipitate is of a type that makes the reaction mixture very viscous and difficult to filter. The purpose of the present invention is to provide a method for the cleavage of 1-ethyl-2-aminomethyl-pyrrolidine without the inherent disadvantages of the method by which tartaric acid is used, i.e. poor yield and optical purity, poor reproducibility, lack of recrystallization and poor crystals.

Foreliggende fremgangsmåte innbefatter spalting av de optiske isomerene av l-etyl-2-aminometyl-pyrrolidin ved dannelse av salter med (-)-di-p-toluoyl-L-vinsyre eller med (+)-di-p-toluoyl-D-vinsyre. The present method includes cleavage of the optical isomers of l-ethyl-2-aminomethyl-pyrrolidine by forming salts with (-)-di-p-toluoyl-L-tartaric acid or with (+)-di-p-toluoyl-D- tartaric acid.

Fire forskjellige diastereomerer oppnås ifølge foreliggende fremgangsmåte. De er ikke tidligere beskrevet i litteraturen: (+)-di-p-toluoyl-D-tartrat av levo l-etyl-2-aminometyl-tyrrolidin, (-)-di-p-toluoyl-L-tartrat av dextro l-etyl-2-aminometyl-pyrrolidin, (-)-di-p-toluoyl-L-tartrat av levo l-etyl-2-aminometyl-pyrrolidin, eller Four different diastereomers are obtained according to the present method. They have not previously been described in the literature: (+)-di-p-toluoyl-D-tartrate of levo l-ethyl-2-aminomethyl-tyrrolidin, (-)-di-p-toluoyl-L-tartrate of dextro l- ethyl-2-aminomethyl-pyrrolidine, (-)-di-p-toluoyl-L-tartrate of levo l-ethyl-2-aminomethyl-pyrrolidine, or

(+)-di-p-toluoyl-D-tartrat av dextro l-etyl-2-aminometyl-pyrrolidin. (+)-di-p-toluoyl-D-tartrate of dextro l-ethyl-2-aminomethyl-pyrrolidine.

Diastereomerene kan fremstilles ved direkte utfelling eller ved en totrinns-prosess. A) Direkte utfelling betyr at én diastereomer isoleres som et krystallinsk salt mens den andre diastereomer forblir oppløst i modervæsken. Det venstredreiende amin utfelles med venstredreiende (-)-di-p-toluoyl-L-vinsyre i en opp-løsning av vann/metanol (foretrukket forhold 1 - 1,2 v/v) og isoleres mens det høyredreiende amin (med (-)-di-p-toluoyl-L-vinsyre) forblir i modervæsken. The diastereomers can be prepared by direct precipitation or by a two-step process. A) Direct precipitation means that one diastereomer is isolated as a crystalline salt while the other diastereomer remains dissolved in the mother liquor. The levorotatory amine is precipitated with levorotatory (-)-di-p-toluoyl-L-tartaric acid in a solution of water/methanol (preferred ratio 1 - 1.2 v/v) and isolated while the dextrorotatory amine (with (- )-di-p-toluoyl-L-tartaric acid) remains in the mother liquor.

Tilsvarende blir det høyredreiende amin utfelt med høyre-dreiende (+)-di-p-toluoyl-D-vinsyre og isolert mens det venstredreiende amin (med (+)-di-p-toluoyl-D-vinsyre) forblir i modervæsken. B) I totrinns-prosessen blir de to diasteriomerene isolert individuelt. Høyredreiende amin utfelles med venstredreiende (-)-di-p-toluoyl-L-vinsyre i en oppløsning av ren metanol, og deretter isolert. Ved tilsetting av vann (forhold vann/metanol 1,0 - 1,5 (v/v)) til metanol-modervæsken oppnås et krystallinsk salt av venstredreiende amin og venstredreiende syre. Similarly, the dextrorotatory amine is precipitated with dextrorotatory (+)-di-p-toluoyl-D-tartaric acid and isolated while the levorotatory amine (with (+)-di-p-toluoyl-D-tartaric acid) remains in the mother liquor. B) In the two-step process, the two diastereomers are isolated individually. The dextrorotatory amine is precipitated with levorotatory (-)-di-p-toluoyl-L-tartaric acid in a solution of pure methanol, and then isolated. By adding water (ratio water/methanol 1.0 - 1.5 (v/v)) to the methanol mother liquor, a crystalline salt of levorotatory amine and levorotatory acid is obtained.

Tilsvarende blir venstredreiende amin utfelt med høyre-dreiende (+)-di-p-toluoyl-D-vinsyre i en oppløsning av ren metanol og ved behandling av metanol-modervæsken med vann oppnås et krystallinsk salt av høyredreiende amin og høyredreiende syre. For å oppnå den optisk aktive l-etyl-2-aminometyl-pyrrolidin behandles den tilsvarende diastereomer ved hjelp av konvensjonell teknikk, dvs. diastereomeren oppløses i vann, mediet gjøres alkalisk, aminet ekstraheres og destilleres. Similarly, levorotatory amine is precipitated with dextrorotatory (+)-di-p-toluoyl-D-tartaric acid in a solution of pure methanol and by treating the methanol mother liquor with water a crystalline salt of dextrorotatory amine and dextrorotatory acid is obtained. To obtain the optically active 1-ethyl-2-aminomethyl-pyrrolidine, the corresponding diastereomer is treated using conventional techniques, i.e. the diastereomer is dissolved in water, the medium is made alkaline, the amine is extracted and distilled.

Ved bruk av foreliggende fremgangsmåte har aminet (-)-l-etyl-2-aminometyl-pyrrolidin blitt fremstilt til en renhet på 96% og gir et utbytte på 85% med (-)-di-p-toluoyl-vinsyre (monohydrat) i en totrinns-prosess. Tilsvarende har (+)-l-etyl-2-aminometyl-pyrrolidin blitt fremstilt til en renhet på 90% og gi et utbytte på 85%. Optiske rensinger kan foretas ved omkrystallisering fra ren metanol eller fra en blanding av metanol og vann. Using the present method, the amine (-)-l-ethyl-2-aminomethyl-pyrrolidine has been prepared to a purity of 96% and gives a yield of 85% with (-)-di-p-toluoyl-tartaric acid (monohydrate) in a two-step process. Similarly, (+)-1-ethyl-2-aminomethyl-pyrrolidine has been prepared to a purity of 90% and give a yield of 85%. Optical purifications can be carried out by recrystallization from pure methanol or from a mixture of methanol and water.

Beste metode for utførelse av oppfinnelsenBest method for carrying out the invention

Følgende illustrerer prinsippene ved og tilpasningen av oppfinnelsen . The following illustrates the principles of and adaptation of the invention.

Eksempel 1 Fremstilling av (-)-di-p-toluoyl-L-tartrat av venstredreiende l-etyl-2-aminometyl-pyrrolidin Example 1 Preparation of (-)-di-p-toluoyl-L-tartrate from levorotatory l-ethyl-2-aminomethyl-pyrrolidine

(direkte metode)(direct method)

60 g (-)-di-p-toluoyl-L-vinsyre (monohydrat) oppløses i 300 ml metanol i en 1-liters trehalset ballongkolbe forsynt med mekanisk røreverk, et termometer og en dråpetrakt. 60 g of (-)-di-p-toluoyl-L-tartaric acid (monohydrate) is dissolved in 300 ml of methanol in a 1-litre three-necked balloon flask fitted with a mechanical stirrer, a thermometer and a dropping funnel.

18,4 g av rasemisk l-etyl-2-aminometyl-pyrrolidin innføres i løpet av 15 minutter igjennom dråpetrakten uten at temperaturen overskrider 30° C. Den transparente oppløsningen hol-des ved 25° C i 15 miniutter, hvoretter ca. 300 ml vann tilsettes i løpet av ca. 30 minutter. Tilsetting av kimkrystaller ved 20-25° C igangsetter krystallisasjon som fortsetter ved romtemperatur i løpet av 1 time. Før filtrering avkjøles suspensjonen til 10° C, og filtratet vaskes med 50 ml is-avkjølt vann. Utbytte: 65%. Renhet = 91% (-)-amin. 18.4 g of racemic 1-ethyl-2-aminomethyl-pyrrolidine are introduced through the dropping funnel within 15 minutes without the temperature exceeding 30° C. The transparent solution is kept at 25° C for 15 minutes, after which approx. 300 ml of water is added during approx. 30 minutes. Addition of seed crystals at 20-25°C initiates crystallization which continues at room temperature within 1 hour. Before filtration, the suspension is cooled to 10° C, and the filtrate is washed with 50 ml of ice-cooled water. Yield: 65%. Purity = 91% (-)-amine.

Fremstilling av saltet av den høyredreiende l-etyl-2-amino-metylforbindelsen foretas på samme måte som beskrevet ovenfor ved utveksling av den venstredreiende syren med den høyre-dreiende syren. Tilsvarende utbytte og renhet oppnås. Preparation of the salt of the dextrorotatory 1-ethyl-2-aminomethyl compound is carried out in the same manner as described above by exchanging the levorotatory acid with the dextrorotatory acid. Corresponding yield and purity are achieved.

Eksempel 2 Fremstilling av (-)-di-p-toluoyl-L-tartrat av høyredreiende og venstredreiende l-etyl-2-amino-metyl-pyrrolidin (totrinns-prosess) Example 2 Preparation of (-)-di-p-toluoyl-L-tartrate from dextrorotatory and levorotatory l-ethyl-2-amino-methyl-pyrrolidine (two-step process)

40 g (-)-di-p-toluoyl-L-vinsyre (monohydrat) oppløses i 120 ml metanol i en 250 ml trehalsetballongkolbe forsynt med et mekanisk røreverk, et termometer og en dråpetrakt. 12,7 g rasemisk l-etyl-2-aminometyl-pyrrolidin innføres under omrøring i løpet av 15 min. gjennom dråpetrakten uten at temperaturen overskrider 20° C. Etter tilsetning av kimkrystaller og avkjøling til 5-15° C utfelles salt av det høyredreiende amin. Etter krystallisering i to timer oppnås 24 g (-)-di-p-toluoyl-L-tartrat av høyredreiende l-etyl-2-aminometyl-pyrrolidin og vaskes med 10 ml isavkjlt metanol. Utbytte: 90%. Renhet = 90% 40 g of (-)-di-p-toluoyl-L-tartaric acid (monohydrate) is dissolved in 120 ml of methanol in a 250 ml three-necked flask fitted with a mechanical stirrer, a thermometer and a dropping funnel. 12.7 g of racemic 1-ethyl-2-aminomethyl-pyrrolidine are introduced with stirring over the course of 15 minutes. through the dropping funnel without the temperature exceeding 20° C. After addition of seed crystals and cooling to 5-15° C, a salt of the dextrorotatory amine is precipitated. After crystallization for two hours, 24 g of (-)-di-p-toluoyl-L-tartrate of dextrorotatory 1-ethyl-2-aminomethyl-pyrrolidine is obtained and washed with 10 ml of ice-cooled methanol. Yield: 90%. Purity = 90%

(+)-amin.(+)-amine.

100 ml vann tilsettes i løpet av 15 minutter til modervæsken som befinner seg ved romtemperatur. Etter tilsetning av kimkrystaller ved romtemperatur utfelles saltet av det venstredreiende amin. Etter krystallisasjon i 2 timer (1 time ved 20° C og 1 time ved 10° C) oppnås 21,9 g (-)-di-p-toluoyl-L-tartrat av venstredreiende. l-etyi-2-aminometyl-pyrrolidin og vaskes med 10 ml isavkjølt vann. Utbytte: 86%. Renhet = 96% 100 ml of water is added over 15 minutes to the mother liquid which is at room temperature. After addition of seed crystals at room temperature, the salt of the levorotatory amine is precipitated. After crystallization for 2 hours (1 hour at 20° C. and 1 hour at 10° C.), 21.9 g of dextrorotatory (-)-di-p-toluoyl-L-tartrate are obtained. 1-ethyl-2-aminomethyl-pyrrolidine and washed with 10 ml of ice-cooled water. Yield: 86%. Purity = 96%

(-)-amin.(-)-amine.

Dersom (+)-di-p-toluoyl-D-vinsyre (monohydrat) anvendes, er fremgangsmåten den samme, men det første saltet som isoleres, If (+)-di-p-toluoyl-D-tartaric acid (monohydrate) is used, the procedure is the same, but the first salt that is isolated,

er (+)-di-p-toluoyl-D-tartrat av venstredreiende l-etyl-2-aminometyl-pyrrolidin og det andre er (+)-di-p-toluoyl-D-tartrat av høyredreiende l-etyl-2-aminometyl-pyrrolidin. is (+)-di-p-toluoyl-D-tartrate of levorotatory l-ethyl-2-aminomethyl-pyrrolidine and the other is (+)-di-p-toluoyl-D-tartrate of dextrorotatory l-ethyl-2- aminomethyl-pyrrolidine.

Eksempel 3 Omkrystallisasjon av (-)-di-p-toluoyl-L-tartratExample 3 Recrystallization of (-)-di-p-toluoyl-L-tartrate

av venstredreiende l-etyl-2-aminometyl-pyrrolidin fra metanol-vann of levorotatory l-ethyl-2-aminomethyl-pyrrolidine from methanol-water

15,7 g av tittelforbindelsen (renhet = 74% (-)-amin) oppløses under oppvarming i 30 ml metanol. Ved romtemperatur tilsettes deretter 30 ml vann til den trehalsede ballongkolben gjennom dråpetrakten. Etter tilsetning av kimkrystaller utfelles tittelforbindelsen og frafiltreres ved 10° C etter 2 timer og vaskes med 5 ml vann. Utbytte: 82%. Renhet = 91% (-)-amin. (-)-di-p-toluoyl-L-tartrat av høyredreiende l-etyl-2-aminometyl-pyrrolidin omkrystalliseres på samme måte. 15.7 g of the title compound (purity = 74% (-)-amine) are dissolved under heating in 30 ml of methanol. At room temperature, 30 ml of water is then added to the three-necked balloon flask through the dropping funnel. After addition of seed crystals, the title compound is precipitated and filtered off at 10° C. after 2 hours and washed with 5 ml of water. Yield: 82%. Purity = 91% (-)-amine. (-)-di-p-toluoyl-L-tartrate of dextrorotatory l-ethyl-2-aminomethyl-pyrrolidine is recrystallized in the same way.

Eksempel 4 Omkrystallisasjon av (+)-di-p-toluoyl-D-tartratExample 4 Recrystallization of (+)-di-p-toluoyl-D-tartrate

av venstredreiende l-etyl-2-aminometyl-pyrrolidin fra metanol of levorotatory l-ethyl-2-aminomethyl-pyrrolidine from methanol

15 g av tittelforbindelsen (renhet = 85% (-)-amin) oppløses under oppvarming i 35 ml metanol. Etter tilsetning av kim- 15 g of the title compound (purity = 85% (-)-amine) are dissolved under heating in 35 ml of methanol. After the addition of germ-

krystaller ved 45 - 50° C utfelles tittelforbindelsen igjen,crystals at 45 - 50° C, the title compound precipitates again,

og etter en krystallisasjonstid på 1 time kan den frafiltreres ved 10° C og vaskes med 10 ml isavkjølt metanol. Utbytte: 80%. Renhet = 96% (-)-amin. (-)-di-p-toluoyl-D-tartrat av høyredreiende l-etyl-2-aminometyl-pyrrolidin omkrystalliseres på samme måte. and after a crystallization time of 1 hour it can be filtered off at 10° C and washed with 10 ml of ice-cooled methanol. Yield: 80%. Purity = 96% (-)-amine. (-)-di-p-toluoyl-D-tartrate of dextrorotatory l-ethyl-2-aminomethyl-pyrrolidine is recrystallized in the same way.

Claims (2)

1. Fremgangsmåte for fremstilling av en diastereomer (+)-di-p-toluoyl-tartrat av levo l-etyl-2-aminometyl-pyrrolidin, (-)-di-p-toluoyl-L-tartrat av dextro l-etyl-2-aminometyl-pyrrolidin, (-)-di-p-toluoyl-L-tartrat av levo l-etyl-2-aminometyl-pyrrolidin, eller (+)-di-p-toluoyl-D-tartrat av dextro l-etyl-2-aminometyl-pyrrolidin, karakterisert ved at rasemisk 1-etyl-2-aminometyl-tyrrolidin oppløses i vanlig metanol og behandles med (-)-di-p-toluoyl-L-vinsyre hvorved (-)-di-p-toluoyl-L-tartrat av levo l-etyl-2-aminometyl-pyrrolidin krystalliseres og isoleres og (-)-di-p-toluoyl-L-tartrat av dextro l-etyl-2-aminometyl-pyrrolidin forblir i modervæsken, eller at den rasemiske l-etyl-2-aminometyl-pyrrolidin behandles med (-)-di-p-toluoyl-L-vinsyre i metanol hvorved (-)-di-p-toluoyl-L-tartrat av dextro l-etyl-2-aminometyl-pyrrolidin krystalliseres og isoleres hvoretter tilsetning av vann til metanol / modervæsken resulterer i krystallisasjon av (-)-di-p-toluoyl-L-tartrat av levo l-etyl-2-aminometyl-pyrrolidin eller at fremgangsmåten for fremstilling av diastereomerene foretas i omvendt rekkefølge ved behandling av rasemisk l-etyl-2-aminometyl-pyrrolidin med (+)-di-p-toluoyl-D-vinsyre .1. Process for the preparation of a diastereomeric (+)-di-p-toluoyl tartrate of levo l-ethyl-2-aminomethyl-pyrrolidine, (-)-di-p-toluoyl-L-tartrate of dextro l-ethyl-2-aminomethyl-pyrrolidine, (-)-di-p-toluoyl-L-tartrate of levo l-ethyl-2-aminomethyl-pyrrolidine, or (+)-di-p-toluoyl-D-tartrate of dextro l-ethyl-2-aminomethyl-pyrrolidine, characterized in that racemic 1-ethyl-2-aminomethyl-tyrrolidin is dissolved in ordinary methanol and treated with (-)-di-p-toluoyl-L-tartaric acid whereby (-)-di-p-toluoyl-L-tartrate of levo l -ethyl-2-aminomethyl-pyrrolidine is crystallized and isolated and (-)-di-p-toluoyl-L-tartrate of dextro l-ethyl-2-aminomethyl-pyrrolidine remains in the mother liquor, or that the racemic l-ethyl-2- aminomethyl-pyrrolidine is treated with (-)-di-p-toluoyl-L-tartaric acid in methanol whereby (-)-di-p-toluoyl-L-tartrate of dextro l-ethyl-2-aminomethyl-pyrrolidine is crystallized and isolated, after which addition of water to methanol / the mother liquor results in crystallization of (-)-di-p-toluoyl-L-tartrate of levo l-ethyl-2-aminomethyl-pyrrolidine or that the procedure for the preparation of the diastereomers is carried out in reverse order by treating racemic l-ethyl-2-aminomethyl-pyrrolidine with ( +)-di-p-toluoyl-D-tartaric acid . 2. Diastereomer, karakterisert ved at den utgjøres av (+)-di-p-toluoyl-D-tartrat av levo l-etyl-2-aminometyl-pyrrolidin, (-)-di-p-toluoyl-L-tartrat av dextro l-etyl-2-aminometyl-pyrrolidin, (-)-di-p-toluoyl-L-tartrat av levo l-etyl-2-aminometyl-pyrrolidin, eller (+)-di-p-toluoyl-D-tartrat av dextro l-etyl-2-aminometyl-pyrrolidin.2. Diastereomer, characterized in that it consists of (+)-di-p-toluoyl-D-tartrate of levo l-ethyl-2-aminomethyl-pyrrolidine, (-)-di-p-toluoyl-L-tartrate of dextro l-ethyl-2-aminomethyl-pyrrolidine, (-)-di-p-toluoyl-L-tartrate of levo l-ethyl-2-aminomethyl-pyrrolidine, or (+)-di-p-toluoyl-D-tartrate of dextro l-ethyl-2-aminomethyl-pyrrolidine.
NO833439A 1982-09-30 1983-09-23 DIASTEROOMER AND PROCEDURE FOR THEIR PREPARATION NO833439L (en)

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FI833512A7 (en) 1984-03-31
DK435283D0 (en) 1983-09-23
ES526077A0 (en) 1984-06-01
SE8205568L (en) 1984-03-31
FI833512L (en) 1984-03-31
CA1210014A (en) 1986-08-19
SE447991B (en) 1987-01-12
SU1240353A3 (en) 1986-06-23
AT377980B (en) 1985-05-28

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