IT9022506A1 - PROCEDURE FOR PREPARING AN INTERMEDIATE - Google Patents
PROCEDURE FOR PREPARING AN INTERMEDIATE Download PDFInfo
- Publication number
- IT9022506A1 IT9022506A1 IT022506A IT2250690A IT9022506A1 IT 9022506 A1 IT9022506 A1 IT 9022506A1 IT 022506 A IT022506 A IT 022506A IT 2250690 A IT2250690 A IT 2250690A IT 9022506 A1 IT9022506 A1 IT 9022506A1
- Authority
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- Italy
- Prior art keywords
- trans
- cis
- formula
- cyclohexanol
- comprises carrying
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 12
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 16
- 239000002904 solvent Substances 0.000 claims description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- 239000011541 reaction mixture Substances 0.000 claims description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- 238000006243 chemical reaction Methods 0.000 claims description 5
- 230000007062 hydrolysis Effects 0.000 claims description 4
- 238000006460 hydrolysis reaction Methods 0.000 claims description 4
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims description 2
- 238000009835 boiling Methods 0.000 claims description 2
- 230000003301 hydrolyzing effect Effects 0.000 claims description 2
- 239000004215 Carbon black (E152) Substances 0.000 claims 1
- 239000012736 aqueous medium Substances 0.000 claims 1
- 229930195733 hydrocarbon Natural products 0.000 claims 1
- 150000002430 hydrocarbons Chemical class 0.000 claims 1
- OQPVMAPWOSNJSD-UHFFFAOYSA-N n-(1-hydroxycyclohexyl)acetamide Chemical compound CC(=O)NC1(O)CCCCC1 OQPVMAPWOSNJSD-UHFFFAOYSA-N 0.000 claims 1
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 6
- 239000000543 intermediate Substances 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 238000011109 contamination Methods 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- HWAFCRWGGRVEQL-UHFFFAOYSA-N n-(4-hydroxycyclohexyl)acetamide Chemical compound CC(=O)NC1CCC(O)CC1 HWAFCRWGGRVEQL-UHFFFAOYSA-N 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 238000010575 fractional recrystallization Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 229910021384 soft carbon Inorganic materials 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
- C07C251/02—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton containing imino groups
- C07C251/04—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton containing imino groups having carbon atoms of imino groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C251/06—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton containing imino groups having carbon atoms of imino groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of a saturated carbon skeleton
- C07C251/08—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton containing imino groups having carbon atoms of imino groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of a saturated carbon skeleton being acyclic
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Steroid Compounds (AREA)
Description
"PROCEDIMENTO PER LA PREPARAZIONE DIUN INTERMEDIO" "PROCEDURE FOR THE PREPARATION OF AN INTERMEDIATE"
TESTO DELLA DESCRIZIONE TEXT OF THE DESCRIPTION
La presente invenzione riguarda la preparazione dell'originale 4-trans-(N-isopropilidene-ammino)-cicloesanolo della formula I The present invention relates to the preparation of the original 4-trans- (N-isopropylidene-amino) -cyclohexanol of formula I
L'originale composto della presente invenzione è un valido intermedio per la preparazione del N-(2-ammino-3,5-dibromobenzU)-trans-4-amminocicloesanolo comunemente noto come ambrosolo. The original compound of the present invention is a valid intermediate for the preparation of N- (2-amino-3,5-dibromobenzU) -trans-4-aminocyclohexanol commonly known as ambrosol.
L'ambrosolo è un agente broncosecretolitico molto notevole e diffuso peril trattamento deltratto respiratorio e deitubibronchiali. Ambrosol is a very notable and widespread bronchosecretolytic agent for the treatment of the respiratory and tubibronchial tract.
In conformità della presente invenzione il4-trans-(N-isopropilidene-ammino)-cicloesanolo della formula Iviene preparato idrolizzando 4-cis/trans-acetammidocicloesanolo della formula II In accordance with the present invention, the 4-trans- (N-isopropylidene-amino) -cyclohexanol of the formula I is prepared by hydrolyzing 4-cis / trans-acetamidocyclohexanol of the formula II
e quindifacendo reagire il4-cis/trans-amminoesanolo della formula ΠΙ and then reacting the 4-cis / trans-aminohexanol of the formula ΠΙ
cosi ottenuto sul posto con acetone e quindi recuperando il prodotto della formula I dalla miscela di reazione. thus obtained in place with acetone and then recovering the product of formula I from the reaction mixture.
L'idrolisi del 4-cis/trans-acetammido cicloesanolo della formula II viene effettuata in presenta di una base forte in un tale solvente che assicura l'omogeneità della miscela di reazione. Preferibilmente si può usare come base idrossido di metallo alcalino e più preferibilmente idrossido di sodio. The hydrolysis of the 4-cis / trans-acetamido cyclohexanol of formula II is carried out in the presence of a strong base in such a solvent which ensures the homogeneity of the reaction mixture. Preferably, alkali metal hydroxide and more preferably sodium hydroxide can be used as the base.
La reazione può essere effettuata entro ampie gamme di temperatura a seconda del solvente o miscela di solventi usati. La gamma di temperatura preferita è da 90 a 120°C. La reazione viene completata entro un periodo da 6 a 18 ore, il 4-cis/trans-acetammidocicloesanolo della formula II viene formato in resa quasi quantitativa entro 8 ore. II prodotto viene portato in un estrattore solvente solvente assieme con il mezzo di reazione. L'estrazione può essere effettuata continuamente con un solvente apolare inerte, preferibilmente con un idrocarburo clorurato. The reaction can be carried out within wide temperature ranges depending on the solvent or mixture of solvents used. The preferred temperature range is 90 to 120 ° C. The reaction is completed within a period of 6 to 18 hours, the 4-cis / trans-acetamidocyclohexanol of formula II is formed in an almost quantitative yield within 8 hours. The product is brought to a solvent extractor together with the reaction medium. The extraction can be carried out continuously with an inert apolar solvent, preferably with a chlorinated hydrocarbon.
Il tempo di estrazione a seconda della quantità e della qualità dei solventi ammonta da 8 a 16 ore e preferibilmente (quando si usa cloroformio) ad 8 ore. The extraction time, depending on the quantity and quality of the solvents, is from 8 to 16 hours and preferably (when using chloroform) to 8 hours.
Quindi il solvente viene distillato via, si aggiunge acetone al 4-cis/transacetammidocicloesanolo e la miscela viene riscaldata al punto di ebollizione della miscela di reazione. Il regime di formazione della base di Schifi è relativamente elevato a questa temperatura ed in condizioni ottimali essa è completata entro due ore. Then the solvent is distilled off, acetone is added to the 4-cis / transacetamidocyclohexanol and the mixture is heated to the boiling point of the reaction mixture. The Schifi base formation rate is relatively high at this temperature and under optimal conditions it is completed within two hours.
Al raffreddamento della miscela di reazione precipita selettivamente il desiderato 4-trans-(N-isopropilideneammino)-cicloesanolo. Il prodotto solido può essere separato per filtrazione a centrifugazione. Upon cooling of the reaction mixture, the desired 4-trans- (N-isopropylideneamino) -cyclohexanol precipitates selectively. The solid product can be separated by centrifugation filtration.
II 4-trans-(N-isopropiIidene-ammino)-cicloesanolo viene ottenuto con buona resa senza alcuna contaminazione di cis-isomero. The 4-trans- (N-isopropiIidene-amino) -cyclohexanol is obtained with good yield without any cis-isomer contamination.
Questa purezza ha grande importanza poiché gli standard di controllo di qualità degli ingredienti farmaceutici permettono in misura sempre minore la presenza di contaminazione derivate da intermedi, materiali di partenza, prodotti laterali e facoltativamente da isomeri. This purity is of great importance as the quality control standards of pharmaceutical ingredients allow less and less the presence of contamination derived from intermediates, starting materials, side products and optionally from isomers.
L'intermedio della produzione di ambrosolo è il 4-trans-amminocicloesanoIo viene separato dalla miscela isomera ci/trans. A causa dei suddetti requisiti di qualità, la formazione di isomeri cis e di sottoprodotti non è desiderata e la loro completa rimozione è un compito molto notevole. The intermediate of ambrosol production is 4-trans-aminocyclohexane. It is separated from the isomeric / trans mixture. Due to the aforementioned quality requirements, the formation of cis isomers and by-products is not desired and their complete removal is a very significant task.
La maniera pratica per sintetizzare l'ambrosolo è quella di usare un materiale di partenza che sia privo di isomero cis in corrispondenza della fase precedente della sintesi a più stadi poiché la purificazione degli intermedi delle seguenti fasi di sintesi richiede molto più lavoro e tempo e risulta in perdite più elevate. The practical way to synthesize ambrosol is to use a starting material that is free of cis isomer at the previous step of the multistage synthesis since the purification of the intermediates of the following synthesis steps requires much more work and time and results in higher losses.
Il 4-ace tammido cicloesanolo può essere preparato da p-acetammidofenolo mediante idrogenazione catalitica (Ber. Dtsch. Chem. Ges. 72, 995/1939/; J. Am. Chem. Soc. 75, 1345 /1953/; Can. J. Chem. 48, 2065/197D/). Il 4-acetammidocicloesanolo è presente nella miscela di reazione sotto forma di isomeri cis e trans a seconda della posizione sierica dei suoi gruppi ammirto e ossidrile. Il rapporto degli isomeri cis-trans formati è da 1:4 a 1:1 a seconda del modo di effettuare la riduzione. 4-acetamido cyclohexanol can be prepared from p-acetamidophenol by catalytic hydrogenation (Ber. Dtsch. Chem. Ges. 72, 995/1939 /; J. Am. Chem. Soc. 75, 1345/1953 /; Can. J . Chem. 48, 2065 / 197D /). 4-acetamidocyclohexanol is present in the reaction mixture in the form of cis and trans isomers depending on the serum position of its admirto and hydroxyl groups. The ratio of the cis-trans isomers formed is from 1: 4 to 1: 1 depending on the way of carrying out the reduction.
La separazione degli isomeri viene risolta mediante cristallizzazione frazionata da differenti solventi (si veda la descrizione del brevetto statunitense N°2.152.26D). I solventi più preferiti sono dietiletere ed acetone. The separation of the isomers is resolved by fractional crystallization from different solvents (see the description of the US patent No. 2,152.26D). The most preferred solvents are diethyl ether and acetone.
In conformità di 1. Am. Chem. Soc. 75, 1345 (1953) il trans-isomero opportunamente puro può essere ottenuto con una resa del 51% dopo ricristallizzazione frazionata 9 volte da ecetone, mentre in conformità del metodo descritto in Can J. Chem. 48, 2065 (1970) il prodotto può essere ottenuto con una resa soltanto del 20-25% dopo ricristallizzazione quattro volte da acetone. In accordance with 1. Am. Chem. Soc. 75, 1345 (1953) the suitably pure trans-isomer can be obtained with a yield of 51% after 9-fold fractional recrystallization from ecetone, while in accordance with the method described in Can J. Chem. 48, 2065 (1970) the product can be obtained with a yield of only 20-25% after recrystallization four times from acetone.
Il 4-acetammido cicloesanolo prreparato con i metodi suddetti comprende una quantità notevole di contaminazione da cis-isomero, come è stato anche provato dagli esperimenti condotti. Questa contaminazione risulta nei corrispondenti cis-intermedi indesiderati nelle fasi successive della sintesi. The 4-acetamido cyclohexanol prepared with the above methods comprises a considerable amount of cis-isomer contamination, as has also been proved by the experiments carried out. This contamination results in the corresponding unwanted cis-intermediates in the later steps of the synthesis.
La presente invenzione viene ulteriormente illustrata dai seguenti esempi non limitativi. The present invention is further illustrated by the following non-limiting examples.
Esempio 1 Example 1
Preparazione del 4-trans-(N-isopropiIidene-ammino)-cicloesanolo Preparation of 4-trans- (N-isopropiIidene-amino) -cyclohexanol
(a) Da 4-cis/trans-acetammidocicioesanolo (a) From 4-cis / trans-acetamidocyiohexanol
160 g (4 moli) di idrossido di sodio vengano sciolti in 640 ml di acqua e quindi si aggiungono 100 (0,64 Moli) di 4-cis-trans-acetammidocicloesanoIo (contenuto del trans- isomero 74%). La miscela viene bollita per 8 are per cui si ottiene una soluzione. Quindi la soluzione viene raffreddata a temperatura ambiente, portata in un estrattore continuo solvente solvente ed estratta con 1200 ml di cloroformio per 8 ore. Le fasi vengono separate, la fase organica viene essiccata su solfato di magnesio anidro, filtrata con carbon dolce e il solvente viene distillato via. 160 g (4 moles) of sodium hydroxide are dissolved in 640 ml of water and then 100 (0.64 moles) of 4-cis-trans-acetamidocyclohexane (content of trans-isomer 74%) are added. The mixture is boiled for 8 ares for which a solution is obtained. The solution is then cooled to room temperature, brought to a continuous solvent solvent extractor and extracted with 1200 ml of chloroform for 8 hours. The phases are separated, the organic phase is dried over anhydrous magnesium sulfate, filtered with charcoal and the solvent is distilled off.
Il 4-cis-trans-amminocicloesanolo greggio cosi ottenuto viene fatto bollire per due ore in 650 ml (8,87 moli) di acetone. Si ottiene una soluzione dalla quale precipita il 4-trans-(N-isopropilidene-ammino)-cicloesanolo al raffreddamento sotto forma di cristalli bianchi. Resa: 45 g (62% calcolato per il transisomero del materiale di partenza). The crude 4-cis-trans-aminocyclohexanol thus obtained is boiled for two hours in 650 ml (8.87 moles) of acetone. A solution is obtained from which 4-trans- (N-isopropylidene-amino) -cyclohexanol precipitates upon cooling in the form of white crystals. Yield: 45 g (62% calculated for the transisomer of the starting material).
Punto di fusione 151°C. Melting point 151 ° C.
(b) Da 4-cis/trans-amminocicIoesanolo (b) From 4-cis / trans-aminocyciohexanol
34,55 g (0,3 Moli) di 4-cis/trans-amminocicloesanolo (contenuto del transisomero 60%) vengono fatti bollire con 220 ml di acetone per due ore. Il 4-trans-(N-isopropilinede-ammino)-cicloesanoio bianco che precipita dalla soluzione viene filtrato via ed essiccato. Così si ottengono 22,72 g (74%) del transisomero puro. Punto di fusione 151°C. 34.55 g (0.3 Mole) of 4-cis / trans-aminocyclohexanol (transisomer content 60%) is boiled with 220 ml of acetone for two hours. The white 4-trans- (N-isopropylinede-amino) -cyclohexanoio precipitating from the solution is filtered off and dried. Thus 22.72 g (74%) of the pure transisomer are obtained. Melting point 151 ° C.
Esempio 2 Example 2
Preparazione del 4-cis/trans-acetammidocicloesanolo di partenza Preparation of the starting 4-cis / trans-acetamidocyclohexanol
4,5 g di catalizzatore di palladio su carbon dolce bagnati con 10% di volume di acqua, 0,6 g (0,006 g male) di acetato di potassio sciolti in 10 ml di acqua e 150 g (0,99 moli) di p-acetammidofenolo vengono caricati in un'autoclave resistente all'acido dotato di un turboagitatore. Il volume della soluzione viene additivato fino a 450 mi. La miscela di reazione viene idrogenata sotto una pressione di 5 bar ad una temperatura di 120-130°C per circa 6 ore. Alla fine della reazione il catalizzatore viene filtrato via e la soluzione acquosa viene evaporata fino a secchezza. Così si ottengono 155,2 g (99%) di prodotto cristallino bianco il cui contenuto di transisomero ammonta al 74%. Punto di fusione 142°C. 4.5 g of palladium catalyst on soft carbon wetted with 10% by volume of water, 0.6 g (0.006 g male) of potassium acetate dissolved in 10 ml of water and 150 g (0.99 mol) of p -acetamide phenol are loaded into an acid-resistant autoclave equipped with a turbo-agitator. The volume of the solution is added up to 450 ml. The reaction mixture is hydrogenated under a pressure of 5 bar at a temperature of 120-130 ° C for about 6 hours. At the end of the reaction the catalyst is filtered off and the aqueous solution is evaporated to dryness. Thus 155.2 g (99%) of white crystalline product are obtained, the transisomer content of which amounts to 74%. Melting point 142 ° C.
Claims (8)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU896744A HU208949B (en) | 1989-12-22 | 1989-12-22 | Process for producing 4-trans-/4-isopropyliden-amino/-cyclohexanol |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| IT9022506A0 IT9022506A0 (en) | 1990-12-21 |
| IT9022506A1 true IT9022506A1 (en) | 1992-06-21 |
| IT1246048B IT1246048B (en) | 1994-11-07 |
Family
ID=10971987
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IT02250690A IT1246048B (en) | 1989-12-22 | 1990-12-21 | PROCEDURE FOR PREPARING AN INTERMEDIATE |
Country Status (5)
| Country | Link |
|---|---|
| JP (1) | JPH0592945A (en) |
| AT (1) | AT398969B (en) |
| GB (1) | GB2239242B (en) |
| HU (1) | HU208949B (en) |
| IT (1) | IT1246048B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19745529C1 (en) * | 1997-10-15 | 1999-03-18 | Great Lakes Chem Konstanz Gmbh | Production of trans-4-amino-cyclohexanol from paracetamol |
| DE10125883A1 (en) | 2001-05-28 | 2002-12-12 | Serumwerk Bernburg Ag | Medicines containing an effector of glutathione metabolism together with alpha-lipoic acid in the context of kidney replacement therapy |
| CN113402402B (en) * | 2021-06-29 | 2023-08-18 | 江西荣兴药业有限公司 | Method for recycling trans-p-aminocyclohexanol from low-concentration waste liquid |
-
1989
- 1989-12-22 HU HU896744A patent/HU208949B/en not_active IP Right Cessation
-
1990
- 1990-12-21 GB GB9027816A patent/GB2239242B/en not_active Expired - Fee Related
- 1990-12-21 IT IT02250690A patent/IT1246048B/en active IP Right Grant
- 1990-12-21 AT AT0261890A patent/AT398969B/en not_active IP Right Cessation
- 1990-12-21 JP JP2412702A patent/JPH0592945A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| GB2239242A (en) | 1991-06-26 |
| ATA261890A (en) | 1994-07-15 |
| AT398969B (en) | 1995-02-27 |
| HU896744D0 (en) | 1990-03-28 |
| IT1246048B (en) | 1994-11-07 |
| HUT58281A (en) | 1992-02-28 |
| GB9027816D0 (en) | 1991-02-13 |
| HU208949B (en) | 1994-02-28 |
| GB2239242B (en) | 1993-07-21 |
| JPH0592945A (en) | 1993-04-16 |
| IT9022506A0 (en) | 1990-12-21 |
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| Date | Code | Title | Description |
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| 0001 | Granted | ||
| TA | Fee payment date (situation as of event date), data collected since 19931001 |
Effective date: 19941228 |