DK146257B - METHOD OF ANALOGUE FOR THE PREPARATION OF (+) - 3R-N-MONOMETHYLAMINO-4C-PHENYL-4T-ETHOXYCARBONYL-CYCLOHEXEN- (1) OR ACID ADDITION SALTS THEREOF - Google Patents
METHOD OF ANALOGUE FOR THE PREPARATION OF (+) - 3R-N-MONOMETHYLAMINO-4C-PHENYL-4T-ETHOXYCARBONYL-CYCLOHEXEN- (1) OR ACID ADDITION SALTS THEREOF Download PDFInfo
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- DK146257B DK146257B DK246275A DK246275A DK146257B DK 146257 B DK146257 B DK 146257B DK 246275 A DK246275 A DK 246275A DK 246275 A DK246275 A DK 246275A DK 146257 B DK146257 B DK 146257B
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Description
(19) DANMARK(19) DENMARK
(12) FREMLÆGGELSESSKRIFT (n)146257B(12) PUBLICATION MANUAL (n) 146257B
DIREKTORATET FOR PATENT- OG VAREMÆRKEVÆSENETDIRECTORATE OF THE PATENT AND TRADEMARKET SYSTEM
(21) Patentansøgning nr.: 2462/75 (51) Int.CI.3: C 07 C101/38 (22) Indleveringsdag: 02 jun 1975 (24) Løbedag: 29 jun 1972 (41) Aim. tilgængelig: 02 jun 1975 (44) Fremlagt: 15 aug 1983 (86) International ansøgning nr.: -(62) Stamansøgning nr.: 3252/72 (30) Prioritet: 30 jun 1971 DE 2132562 (71) Ansøger: «WARNER-LAMBERT COMPANY; Morris Plains, US.(21) Patent Application No: 2462/75 (51) Int.CI.3: C 07 C101 / 38 (22) Filing Date: 02 Jun 1975 (24) Running Date: 29 Jun 1972 (41) Aim. available: 02 Jun 1975 (44) Submitted: 15 Aug 1983 (86) International Application No: - (62) Stock Application No .: 3252/72 (30) Priority: 30 Jun 1971 DE 2132562 (71) Applicant: «WARNER- LAMBERT COMPANY; Morris Plains, US.
(72) Opfinder: Gerhard «Satzinger; DE, Wolfgang Dieter «Herrmann; DE, Manfred Franz Relnhold «Herrmann; DE.(72) Inventor: Gerhard «Satzinger; DE, Wolfgang Dieter «Herrmann; DE, Manfred Franz Relnhold «Herrmann; THE.
(74) Fuldmægtig: Ingeniørfirmaet Budde, Schou A Co_ (54) Analogifremgangsmåde til fremstilling af (+)-3r-N-monomethylamino-4c-phenyl-4t-ethoxycar-bonyl-cyclohexen-(1) eller syreadditionssalte deraf(74) Plenipotentiary: Engineer Budde, Schou A Co_ (54) Analogous Process for the Preparation of (+) - 3r-N-Monomethylamino-4c-phenyl-4t-ethoxycarbonyl-cyclohexene- (1) or Acid Addition Salts thereof
Den foreliggende opfindelse angår en analogifrexngangsmåde til fremstilling af den hidtil ukendte forbindelse (+)-3r-N-monomethyl-amino-4c-phenyl-4t-ethoxycarbonyl-cyclohexen-(1) med formlen D CH,The present invention relates to an analogous process for the preparation of the novel compound (+) - 3r-N-monomethylamino-4c-phenyl-4t-ethoxycarbonyl-cyclohexene- (1) of formula D CH
* I H* I H
S „/V/ /OOC2H5S / V / / OOC2H5
0 rrC0 rrC
1 [P1 [P.
eller syreadditionssalte deraf.or acid addition salts thereof.
2 1462572 146257
Fra beskrivelsen til dansk patentansøgning nr. 1010/71 kendes en fremgangsmåde til fremstilling af 3r-N-monomethylamino-4c-phenyl-4t--ethoxycarbonyl-cyclohexen-(1), som har kraftig analgetisk virkning.From the specification of Danish Patent Application No. 1010/71, a process for the preparation of 3r-N-monomethylamino-4c-phenyl-4t-ethoxycarbonyl-cyclohexene- (1) is known which has a strong analgesic effect.
Fremgangsmåden ifølge opfindelsen er ejendommelig ved, at DL-3r-N-monomethylamino-4c-phenyl-4t-ethoxycarbonyl-cyclohexen-(1) med formlen CH- I 3The process of the invention is characterized in that DL-3r-N-monomethylamino-4c-phenyl-4t-ethoxycarbonyl-cyclohexene- (1) of the formula CH-3
N HN H
C00CoHc /\2 5 omsættes med (+)-0,0-dibenzoyl-L-vinsyre eller {-)-0,0-dibenzoyl-D--vinsyre til dannelse af diastereomere salte, som derpå underkastes fraktioneret krystallisation til fraskillelse af det diastereomere salt af (+)-3r-N-monomethylamino-4c-phenyl-4t-ethoxycarbonyl-cyclo-hexen-(l), og om ønsket (+)-3r-N-monomethylamino-4c-phenyl-4t-ethoxy-carbonyl-cyclohexen-(1) frigøres ved behandling med base, og den dannede forbindelse eventuelt overføres i et syreadditionssalt deraf.C00 COhc / reaction is reacted with (+) - 0,0-dibenzoyl-L-tartaric acid or {-) - 0,0-dibenzoyl-D - tartaric acid to form diastereomeric salts, which are then subjected to fractional crystallization to separate it. diastereomeric salt of (+) - 3r-N-monomethylamino-4c-phenyl-4t-ethoxycarbonyl-cyclohexene- (1), and if desired (+) - 3r-N-monomethylamino-4c-phenyl-4t-ethoxy- carbonyl-cyclohexene- (1) is released by treatment with base, and the compound formed is optionally transferred into an acid addition salt thereof.
Ved fremgangsmåden omsættes den racemiske DL-3r-N-monomethyl-amino-4c-phenyl-4t-ethoxycarbonyl-cyclohexen-(1) på i og for sig kendt måde, dvs. ved hjælp af (+)-0,0-dibenzoyl-L-vinsyre eller (-)-0,0-dibenzoyl-D-vinsyre i acetone, lavere alkoholer såsom methanol, ethanol og isopropanol eller i vand, hvorefter de således fremstillede diastereomere salte underkastes fraktioneret krystallisation som udnytter deres forskellige opløseligheder i de anvendte opløsningsmidler, og om ønsket basen frigøres fra det rene diastereomere salt af (+)-3r-N-monomethylamino-4c-phenyl-4t-ethoxycarbonyl-cyclohexen--(1) ved behandling med vandig alkalihydroxid eller ammoniumhydroxid og den fri base eventuelt overføres i hydrochloridet eller et andet syreadditionssalt på i og for sig kendt måde med hydrogenchloridgas eller den til det ønskede syreadditionssalt svarende syre i egnede opløsningsmidler, f.eks. ethylacetat. Anvendelsen af (+)-0,0-di-benzoyl-L-vinsyre eller (-)-0,0-dibenzoyl-D-vinsyre til racematadskillelse har vist sig at være særligt velegnet til dette formål, da den første danner et tungtopløseligt salt, som kan fås optisk rent ved omkrystallisation, med den ønskede farmakologisk aktive højredrejende enantiomere base. Den anden danner et tungtopløseligt salt med den venstredrejende enantiomere base, således at den ønskede højredrejende base kan fås fra moderluden. I først- 3 146257 nævnte tilfælde fås den farmakologiske aktive forbindelse således direkte i ren krystallinsk form (jfr. eks. 2 nedenfor), medens man i sidstnævnte tilfælde må foretage to krystallisationer (jfr. eks. la), b) og c) nedenfor).In the process, the racemic DL-3r-N-monomethyl-amino-4c-phenyl-4t-ethoxycarbonyl-cyclohexene- (1) is reacted in a manner known per se, i.e. by (+) - 0,0-dibenzoyl-L-tartaric acid or (-) - 0,0-dibenzoyl-D-tartaric acid in acetone, lower alcohols such as methanol, ethanol and isopropanol or in water, and the diastereomers thus prepared salts are subjected to fractional crystallization which utilizes their various solubilities in the solvents used and, if desired, the base is released from the pure diastereomeric salt of (+) - 3r-N-monomethylamino-4c-phenyl-4t-ethoxycarbonyl-cyclohexene - (1) treatment with aqueous alkali hydroxide or ammonium hydroxide and the free base is optionally transferred into the hydrochloride or another acid addition salt in a manner known per se with hydrogen chloride gas or the acid acid salt corresponding to the desired acid in suitable solvents, e.g. ethyl acetate. The use of (+) - 0,0-di-benzoyl-L-tartaric acid or (-) - 0,0-dibenzoyl-D-tartaric acid for racial separation has been found to be particularly suitable for this purpose, as the first forms a highly soluble salt, which can be obtained optically pure by recrystallization, with the desired pharmacologically active right-turning enantiomeric base. The other forms a heavily soluble salt with the left-turn enantiomeric base, so that the desired right-turning base can be obtained from the mother liquor. Thus, in the first mentioned case, the pharmacologically active compound is obtained directly in pure crystalline form (cf. example 2 below), while in the latter case two crystallizations (cf. examples 1a), b) and c) below must be made. ).
Det har overraskende vist sig, at (+)-3r-N-monomethylamino~ -4c-phenyl-4t-ethoxycarbonyl-cyclohexen-(1)-HC1 ("D-HC1") ved dyreforsøg ved subcutan, intravenøs og intragastrisk indgift udviser kraftigere analgetisk virkning og tillige mere fordelagtige terapeutiske egenskaber end det er tilfældet med DL-3r-N-monomethylamino-4c-phenyl--4t-ethoxycarbonyl-cyclohexen-(1) ("DL-HC1"). Disse fordelagtige egenskaber er naturligvis ikke afhængige af den til saltdannelsen specifikt anvendte syre, men skyldes egenskaberne ved (+)-basen eller dens kation.Surprisingly, it has been found that (+) - 3r-N-monomethylamino ~ -4c-phenyl-4t-ethoxycarbonyl-cyclohexene- (1) -HCl ("D-HCl") in animal studies at subcutaneous, intravenous and intragastric administration stronger analgesic effect and also more advantageous therapeutic properties than is the case with DL-3r-N-monomethylamino-4c-phenyl-4t-ethoxycarbonyl-cyclohexene- (1) ("DL-HCl"). Of course, these beneficial properties do not depend on the acid specifically used for salt formation, but are due to the properties of the (+) base or its cation.
Med henblik på anvendelse kan forbindelsen formuleres med konventionelle farmaceutiske bærestoffer til dannelse af typiske orale eller rektale dosisenheder såsom tabletter, kapsler, opløsninger, suppositorier og lignende. En voksen person kan gives fra ca. 5 til ca.For use, the compound may be formulated with conventional pharmaceutical carriers to form typical oral or rectal dosage units such as tablets, capsules, solutions, suppositories and the like. An adult can be given from approx. 5 to approx.
30 mg af disse forbindelser op til tre gange daglig, og der kan naturligvis gives mindre doser til børn.30 mg of these compounds up to three times daily, and of course, smaller doses can be given to children.
I det følgende beskrives bestemmelsen af forbindelsens akutte toksicitet og dens analgetiske virkning.The following describes the determination of the acute toxicity of the compound and its analgesic effect.
Til bestemmelse af den akutte toksicitet anvendes hanmus (NMRI) med en vægt på 20-27 g som forsøgsdyr. Alle forsøgsdyrene fastes i 16-18 timer inden forsøgets start. De har fri adgang til vand. Hver forsøgsgruppe består af 6 dyr. Dosis forøges med en faktor på 1,3.To determine the acute toxicity, male mice (NMRI) weighing 20-27 g are used as experimental animals. All test animals are fasted for 16-18 hours before the start of the trial. They have free access to water. Each experimental group consists of 6 animals. The dose is increased by a factor of 1.3.
Det anvendte væskevolumen udgør 2 ml pr. 100 g legemsvægt ved intragastrisk indgift og 1 ml pr. 100 g legemsvægt ved subcutan og intravenøs indgift. Observationerne foretages over 7 dage. Statistisk bedømmelse af forsøgsresultaterne foretages i overensstemmelse med fremgangsmåden ifølge Litchfield and Wilcoxon, jf. Ther, Grundlagen der experim. Arzneimittelforschung, S. 82, Wiss. Verlagsgesellschaft, Stuttg. 1965.The volume of liquid used is 2 ml. 100 g of body weight by intragastric administration and 1 ml per ml. 100 g body weight by subcutaneous and intravenous administration. The observations are made over 7 days. Statistical evaluation of the experimental results is carried out in accordance with the method of Litchfield and Wilcoxon, cf. Ther, Grundlagen der experiment. Drug Research, S. 82, Wiss. Publishing Company, Stuttg. 1965th
Den analgetiske virkning bestemmes ved phenyl-p-quinon-prøven. Hver forsøgsgruppe består af 12 hanmus (NMRI), som vejer 17-23 g. Der indgives intraperitonealt 1,25 ml af en 0,02%'s phenyl-p-quinonopløs-ning pr. 100 g legemsvægt ved 15 og 30 minutter efter indgiften af forsøgsstoffet. Ved de intravenøse forsøg injiceres phenyl-p-quinon umiddelbart efter indgiften af stoffet. Kun sådanne dyr, som ikke udviser typiske smertereaktioner i løbet af de efterfølgende 20 minutter, betragtes som værende beskyttet. Forsøget kasseres, såfremt ikke mindst 4 146257 11 ud af 12 dyr i kontrolgruppen reagerer. Også i det foreliggende tilfælde foretages der statistisk bedømmelse af forsøgsresultaterne ifølge Litchfield og Wilcoxon's metode.The analgesic effect is determined by the phenyl-β-quinone test. Each experimental group consists of 12 male mice (NMRI) weighing 17-23 g. Intraperitoneally 1.25 ml of a 0.02% phenyl-β-quinone solution is administered per day. 100 g of body weight at 15 and 30 minutes after administration of the test substance. In the intravenous trials, phenyl-β-quinone is injected immediately after administration of the drug. Only such animals that do not exhibit typical pain reactions during the subsequent 20 minutes are considered to be protected. The experiment is discarded if at least 4 out of 12 animals in the control group respond. Also in the present case, statistical evaluation of the test results according to Litchfield and Wilcoxon's method is performed.
Resultaterne af de ovenfor beskrevne forsøg er anført i denThe results of the experiments described above are given in it
ÆDAED
følgende tabel. Det morfinlignende analgetiske meperidin ("Dolan tin "'i-') som for tiden er det førende stof på markedet, anvendes som det positive standardstof. Til sammenligning er medtaget resultaterne for beslægtede cyclohexen-forbindelser.the following table. The morphine-like analgesic meperidine ("Dolan tin" 'i-'), currently the leading substance on the market, is used as the positive standard drug. For comparison, the results for related cyclohexene compounds are included.
5 146257 ω -η ό 4-1 r-i m SO n O m O η -ό· sf r- r- O n cn co ·3* ro n <1)4301------ - - - - - - - - - - ft Η O "tf r-4 CM n 'tt' CO O O Ί1 2 3 01 (O CM CO 10 (OO h <j r-i n h η n ιο h nr- η o1 H IH -4 0)5 146257 ω -η ό 4-1 ri m SO n O m O η -ό · sf r- r- O n cn co · 3 * ro n <1) 4301 ------ - - - - - - - - - - ft Η O "tf r-4 CM n 'tt' CO OO Ί1 2 3 01 (O CM CO 10 (OO h <j ri nh η n ιο h nr- η o1 H IH -4 0)
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6 1462576 146257
Fremgangsmåden ifølge opfindelsen forklares nærmere i de følgende eksempler.The process according to the invention is explained in more detail in the following examples.
Eksempel 1 a) 259,4 g, 1 mol, DL-3r-N-monomethylamino-4c-phenyl-4t-ethoxy-carbonyl-cyclohexen-(1) opløses i 0,5 liter acetone og blandes ved stuetemperatur med en blanding af 375,3 g, 1 mol, (-)-0,0-dibenzoyl--D-vinsyre-monohydrat i 1,5 liter acetone. Efter henstand natten over frafiltreres det dannede bundfald. Det består hovedsagelig af (-)-3r-N-monomethylamino-4c-phenyl-4t-ethoxycarbonyl-cyclohexen-(1) --dibenzoyl-D-tartrat. Filtratet inddampes til tørhed. Den krystallinske remanens optages i vand, basen frigøres med ammoniakopløsning og ekstraheres med benzin. Efter tørring af den organiske base med vandfri natriumsulfat sidestilleres opløsningsmidlet. Der fås en remanens på 104 g (+)-3r-N-monomethylamino-4c-phenyl-4t-ethoxycarbo-nyl-cyclohexen-(1) i form af en farveløs olie, [a]^ +355 (5 g/100 ml methanol).Example 1 a) 259.4 g, 1 mole, DL-3r-N-monomethylamino-4c-phenyl-4t-ethoxy-carbonyl-cyclohexene- (1) are dissolved in 0.5 liter of acetone and mixed at room temperature with a mixture of 375.3 g, 1 mole, (-) - 0,0-dibenzoyl-D-tartaric acid monohydrate in 1.5 liters of acetone. After standing overnight, the resulting precipitate is filtered off. It consists mainly of (-) - 3r-N-monomethylamino-4c-phenyl-4t-ethoxycarbonyl-cyclohexene- (1) -dibenzoyl-D-tartrate. The filtrate is evaporated to dryness. The crystalline residue is taken up in water, the base is released with ammonia solution and extracted with gasoline. After drying the organic base with anhydrous sodium sulfate, the solvent is equilibrated. A residue of 104 g (+) - 3r-N-monomethylamino-4c-phenyl-4t-ethoxycarbonyl-cyclohexene (1) in the form of a colorless oil is obtained, [a] +355 (5 g / 100 ml of methanol).
b) Med henblik på udfældning af hydrochloridet opløses 100 g, 0,385 mol, af (+)-basen fremstillet ovenfor under a) i 400 ml vandfri ethylacetat, og der tilsættes dråbevis en opløsning af 14 g, 0,385 mol, HC1 i 400 ml ethylacetat under omrøring ved stuetemperatur. Efter afkøling frasuges bundfaldet og vaskes med ethylacetat.(b) To precipitate the hydrochloride, dissolve 100 g, 0.385 mol, of the (+) base prepared above under (a) in 400 ml of anhydrous ethyl acetate, and dropwise add a solution of 14 g, 0.385 mol, HCl in 400 ml of ethyl acetate. with stirring at room temperature. After cooling, the precipitate is aspirated and washed with ethyl acetate.
Udbytte: 97 g, 85% af det teoretiske udbytte (+)-3r-N-mono~ methylamino-4c-phenyl-4t-ethoxycarbonyl-cyclohexen-(1)-hydrochlorid. Farveløse krystaller med smp. 210-212°C, [a]^ +315° (10 g/100 ml vand).Yield: 97 g, 85% of theory (+) - 3r-N-mono-methylamino-4c-phenyl-4t-ethoxycarbonyl-cyclohexene (1) hydrochloride. Colorless crystals with m.p. 210-212 ° C, [α] 25 + 315 ° (10 g / 100 ml water).
c) 26 g, 0,1 mol, (+)-3r-N-monomethylamino-4c-phenyl-4t- -ethoxycarbonyl-cyclohexen-(1) opløses i 100 ml acetone, og til denne opløsning sættes en opløsning af 37,6 g, 0,1 mol, (-)-0,0-dibenzoyl- -D-vinsyre-monohydrat i 100 ml acetone. Det dannede bundfald frafil- 24 o treres. Der fås 20,2 g salt med [a]D +78 (10 g/100 ml methanol).c) dissolve 26 g, 0.1 mol, (+) - 3r-N-monomethylamino-4c-phenyl-4t- -ethoxycarbonyl-cyclohexene- (1) in 100 ml of acetone, and to this solution is added a solution of 37, 6 g, 0.1 mole, (-) - 0.0-dibenzoyl-D-tartaric acid monohydrate in 100 ml of acetone. The precipitate formed is filtered off 24 hours. 20.2 g of salt are obtained with [a] D +78 (10 g / 100 ml of methanol).
Saltet omkrystalliseres to gange af en lille mængde methanol. Produktet udgør da 8,5 g (+)-3r-N-monomethylamino-4c-phenyl-4t-ethoxycarbo-nyl-cyclohexen-(1)-0,0-dibenzoyl-D-tartrat i form af farveløse krystaller med smp. 113°C og [a]^4 +86,5° (10 g/100 ml methanol).The salt is twice recrystallized from a small amount of methanol. The product then constitutes 8.5 g (+) - 3r-N-monomethylamino-4c-phenyl-4t-ethoxycarbonyl-cyclohexene- (1) -0,0-dibenzoyl-D-tartrate in the form of colorless crystals, m.p. 113 ° C and [α] 4 + 86.5 ° (10 g / 100 ml methanol).
Eksempel 2 26 g, 0,1 mol, DL-3r-N-monomethylamino-4c-phenyl-4t-ethoxy-carbonyl-cyclohexen-(1) opløses i 50 ml acetone, og der tilsættes en 7 146257 opløsning af 37,6 g, 0,1 mol, (+)-0,0-dibenzoyl-L-vinsyre-monohydrat i 150 ml acetone ved stuetemperatur. Efter henstand natten over fra-filtreres bundfaldet og vaskes med en lille mængde acetone. Det rå produkt udgør 32,3 g med smp. 175-176°C og [a]p2 +208,5° (2 g/100 ml methanol). Saltet omkrystalliseres af 500 ml methanol, hvorved der fås 22 g (+)-3r-monomethylamino-4c-phenyl-4t-ethoxycarbonyl-cyclo-hexen-(1)-0,0-dibenzoyl-L-tartrat med smp. 185-186°C og [a]22 +220° (2 g/100 ml methanol).Example 2 26 g, 0.1 mol, DL-3r-N-monomethylamino-4c-phenyl-4t-ethoxy-carbonyl-cyclohexene (1) are dissolved in 50 ml of acetone and a solution of 37.6 is added. g, 0.1 mole, (+) - 0.0-dibenzoyl-L-tartaric acid monohydrate in 150 ml of acetone at room temperature. After standing overnight, the precipitate is filtered off and washed with a small amount of acetone. The crude product is 32.3 g with m.p. 175-176 ° C and [a] p 2 + 208.5 ° (2 g / 100 ml methanol). The salt is recrystallized from 500 ml of methanol to give 22 g of (+) - 3r-monomethylamino-4c-phenyl-4t-ethoxycarbonyl-cyclohexene- (1) -0,0-dibenzoyl-L-tartrate, m.p. 185-186 ° C and [α] 22 + 220 ° (2 g / 100 ml methanol).
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DK246275A DK146257C (en) | 1971-06-30 | 1975-06-02 | METHOD OF ANALOGUE FOR THE PREPARATION OF (+) - 3R-N-MONOMETHYLAMINO-4C-PHENYL-4T-ETHOXYCARBONYL-CYCLOHEXEN- (1) OR ACID ADDITION SALTS THEREOF |
Applications Claiming Priority (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE2132562 | 1971-06-30 | ||
DE19712132562 DE2132562C (en) | 1971-06-30 | (+) 3r N monomethylamino 4c phenyl 4t athoxycarbonyl cyclohexene (1), its D or L O, O dibenzoyl tartrate, hydro chloride or other salts of physiologically harmless acids and processes for their production | |
DK325272A DK134752C (en) | 1971-06-30 | 1972-06-29 | ANALOGICAL PROCEDURE FOR THE PREPARATION OF (+) - 3R-N-MONOMETHYL-AMINO-4C-PHENYL-4T-ETHOXYCARBONYL-CYCLOHEXENE (1) OR ACID ADDITION SALTS THEREOF |
DK325272 | 1972-06-29 | ||
DK246275 | 1975-06-02 | ||
DK246275A DK146257C (en) | 1971-06-30 | 1975-06-02 | METHOD OF ANALOGUE FOR THE PREPARATION OF (+) - 3R-N-MONOMETHYLAMINO-4C-PHENYL-4T-ETHOXYCARBONYL-CYCLOHEXEN- (1) OR ACID ADDITION SALTS THEREOF |
Publications (3)
Publication Number | Publication Date |
---|---|
DK246275A DK246275A (en) | 1975-09-15 |
DK146257B true DK146257B (en) | 1983-08-15 |
DK146257C DK146257C (en) | 1984-01-23 |
Family
ID=27183526
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DK246275A DK146257C (en) | 1971-06-30 | 1975-06-02 | METHOD OF ANALOGUE FOR THE PREPARATION OF (+) - 3R-N-MONOMETHYLAMINO-4C-PHENYL-4T-ETHOXYCARBONYL-CYCLOHEXEN- (1) OR ACID ADDITION SALTS THEREOF |
Country Status (1)
Country | Link |
---|---|
DK (1) | DK146257C (en) |
-
1975
- 1975-06-02 DK DK246275A patent/DK146257C/en not_active IP Right Cessation
Also Published As
Publication number | Publication date |
---|---|
DK246275A (en) | 1975-09-15 |
DK146257C (en) | 1984-01-23 |
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