EP0504351A1 - Procede pour la fabrication de 4-aryle-2-pyrrolidinones optiquement actifs - Google Patents
Procede pour la fabrication de 4-aryle-2-pyrrolidinones optiquement actifsInfo
- Publication number
- EP0504351A1 EP0504351A1 EP91917189A EP91917189A EP0504351A1 EP 0504351 A1 EP0504351 A1 EP 0504351A1 EP 91917189 A EP91917189 A EP 91917189A EP 91917189 A EP91917189 A EP 91917189A EP 0504351 A1 EP0504351 A1 EP 0504351A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- optically active
- formula
- aryl
- pyrrolidinones
- compound
- Prior art date
- Legal status (The legal status 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 status listed.)
- Withdrawn
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic 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
- C07D207/18—Heterocyclic 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 one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic 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 one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D263/16—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D263/18—Oxygen atoms
- C07D263/20—Oxygen atoms attached in position 2
- C07D263/26—Oxygen atoms attached in position 2 with hetero atoms or acyl radicals directly attached to the ring nitrogen atom
Definitions
- the invention relates to the process for the preparation of optically active 4-aryl-2-pyrrolidinones and the process for the preparation of the optically active starting compounds which are suitable as intermediates for the preparation of the 4S or 4R enantiomers of 4-aryl-2-pyrrolidinones.
- the desired (4S) - or (4R) -4-aryl-2-pyrrolidinones can be prepared from the easily accessible optically active starting compounds in a simple synthesis and can be isolated in high optical purity and good yield without expensive separation operations.
- the recovery of the auxiliary is to be regarded as an additional advantage of the method according to the invention.
- the invention relates to the process for producing (4S) - or
- R 1 is hydrogen or a hydrocarbon radical with up to 7 carbon atoms and R 2 C 1-4 alkyl which is optionally interrupted by an oxygen atom, characterized in that an optically active compound of the formula II
- R 1 has the meaning of R1 or represents an easily removable group
- R 2 is C 1-4 alkyl
- Suitable hydrocarbon radicals R 1 are saturated or unsaturated, straight-chain or branched alkyl groups with 1-6 carbon atoms, preferably 1-4 carbon atoms, furthermore C 4-6 cycloalkylalkyl and cycloalkyl groups with 3-7 carbon atoms and the benzyl group and cycloalkyl groups interrupted by an oxygen atom.
- saturated alkyl groups are, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec. Butyl, tert. Butyl, pentyl, 2,2-dimethylpropyl and hexyl suitable.
- alkenyl and alkynyl groups 2-propenyl, 2-propionyl.
- hydrocarbon radical R 1 is a cycloalkyl group, it means cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl, preferably C 3-5 cycloalkyl groups. Cyclopropylmethyl, cyclopropylethyl and cyclopentylmethyl are to be regarded as preferred for the cycloalkyl-alkyl group.
- hydrocarbon radical is interrupted by an oxygen atom
- a further asymmetry center can be present, which can be converted into the antipodes in the usual way.
- the term “easily removable group” means that the hydroxyl protective group can be easily removed either under the reaction conditions or subsequently in the customary manner.
- the protecting groups include, for example, the methoxymethyl, methoxyethoxymethyl and also the benzyl group.
- the commonly used hydrogenation catalysts such as, for example, are suitable as catalysts for the reaction according to the invention Raney nickel or precious metal catalysts such as platinum oxide and palladium / carbon.
- the reaction takes place at room temperature or with heating to 50 ° C. under normal hydrogen pressure or elevated hydrogen pressure (approx. 50 bar) in an aqueous suspension or in inert solvents such as alcohols, esters or ketones or mixtures thereof.
- the reaction is generally complete after 1 to 10 hours.
- the etherification is carried out by reaction with a corresponding tosylate, mesylate or halide in the presence of a base such as alkali metal hydroxides and carbonates and tetrabutylammonium hydrogen sulfate in inert solvents such as dimethyl sulfoxide, dimethylformamide, acetonitrile, tetrahydrofuran, methylene chloride or alcohols at room temperature to the boiling point of the solvent.
- a base such as alkali metal hydroxides and carbonates and tetrabutylammonium hydrogen sulfate
- inert solvents such as dimethyl sulfoxide, dimethylformamide, acetonitrile, tetrahydrofuran, methylene chloride or alcohols at room temperature to the boiling point of the solvent.
- the invention further relates to the compounds of formula II, which are optically active starting compounds, from which the compounds of formula I are obtained with very high optical purity in one reaction step.
- the invention also relates to the process for the preparation of the compounds of formula II, characterized in that an optically active
- the addition takes place in the manner of a Michael addition, by forming the enolate amone of compound III with strong bases and adding it to the olefin.
- the reaction takes place at low temperatures (- 110 ° C to - 40 ° C) in aprotic solvents such as cyclic ethers, for example dioxane or tetrahydrofuran.
- aprotic solvents such as cyclic ethers, for example dioxane or tetrahydrofuran.
- the bases are, for example, alkali salts such as
- the antipode is obtained after the addition of the olefin in good yields and high optical purity after recrystallization.
- the starting compound of formula III can be prepared by acetylation of (4S) - or (4R) -4-benzyl-2-oxazolidinone by customary methods.
- the acetylation can for example in the presence of strong bases such as butyllithium, lithium diisopropylamide, NaH and. a. in aprotic solvents such as cyclic ethers or hydrocarbons or in a two-phase system according to the method described by V. Illi Synthesis 1979, 387.
- the starting compounds of the formula IV can be synthesized, for example, by aldol condensation of the aldehyde with nitromethane (C.B. Gairand, G.R. Lappin 1. Org. Chem. 18, 1 (1953).
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Procédé stéréosélectif pour la fabrication de (4R)- ou (4S)-4-Aryle-2-pyrrolidinones de formule (I) où R1 représente l'oxygène ou, le cas échéant, un radical d'hydrocarbure interrompu par un atome d'oxygène et ayant jusqu'à 7 atomes de carbone, et où R2 représente un groupe alkyle C1-4. L'invention concerne également des produits intermédiaires et le procédé stéréosélectif pour la fabrication des produits intermédiaires optiquement actifs.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE4032055A DE4032055A1 (de) | 1990-10-05 | 1990-10-05 | Verfahren zur herstellung von optisch aktiven 4-aryl-2-pyrrolidinonen |
DE4032055 | 1990-10-05 |
Publications (1)
Publication Number | Publication Date |
---|---|
EP0504351A1 true EP0504351A1 (fr) | 1992-09-23 |
Family
ID=6415955
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP91917189A Withdrawn EP0504351A1 (fr) | 1990-10-05 | 1991-09-27 | Procede pour la fabrication de 4-aryle-2-pyrrolidinones optiquement actifs |
Country Status (6)
Country | Link |
---|---|
US (1) | US5298628A (fr) |
EP (1) | EP0504351A1 (fr) |
JP (1) | JPH05502895A (fr) |
CA (1) | CA2070653A1 (fr) |
DE (1) | DE4032055A1 (fr) |
WO (1) | WO1992006077A1 (fr) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE10038355A1 (de) | 2000-08-05 | 2002-02-28 | Mengel & Kuehlborn Geraetebau | Torabdichtung einer Verladeöffnung eines Gebäudes |
EP2066174B1 (fr) | 2006-09-12 | 2017-11-08 | Beth Israel Deaconess Medical Center, Inc. | Compositions contenant de l'alpha-1-antitrypsine et leurs procédés d'utilisation |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE2413935A1 (de) * | 1974-03-20 | 1975-10-16 | Schering Ag | 4-(polyalkoxy-phenyl)-2-pyrrolidone |
US4193926A (en) * | 1974-03-20 | 1980-03-18 | Schering Aktiengesellschaft | 4-(Polyalkoxy phenyl)-2-pyrrolidones |
DE2541855A1 (de) * | 1975-09-18 | 1977-03-31 | Schering Ag | 4-(polyalkoxy-phenyl)-2-pyrrolidone ii |
-
1990
- 1990-10-05 DE DE4032055A patent/DE4032055A1/de not_active Withdrawn
-
1991
- 1991-09-27 CA CA002070653A patent/CA2070653A1/fr not_active Abandoned
- 1991-09-27 JP JP3515441A patent/JPH05502895A/ja active Pending
- 1991-09-27 EP EP91917189A patent/EP0504351A1/fr not_active Withdrawn
- 1991-09-27 US US07/877,181 patent/US5298628A/en not_active Expired - Fee Related
- 1991-09-27 WO PCT/DE1991/000773 patent/WO1992006077A1/fr not_active Application Discontinuation
Non-Patent Citations (1)
Title |
---|
See references of WO9206077A1 * |
Also Published As
Publication number | Publication date |
---|---|
JPH05502895A (ja) | 1993-05-20 |
US5298628A (en) | 1994-03-29 |
WO1992006077A1 (fr) | 1992-04-16 |
CA2070653A1 (fr) | 1992-04-06 |
DE4032055A1 (de) | 1992-04-09 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP1844039B1 (fr) | Derives de quinoline et d'isoquinoline 5-substitues, procede permettant de les produire et leur utilisation comme antiphlogistique | |
EP0241003B1 (fr) | Dérivés de 4H-1-benzopyran-4-one, procédé pour leur préparation et leur utilisation comme médicaments | |
DE2453648B2 (de) | Verfahren zur Herstellung von 1 a -Hydroxycholesterinen sowie 1 alpha , 2 a -Epoxy-6 ß sulfonyloxyderivate des S a -Cholestan-3-ons als Zwischenprodukte | |
CH621115A5 (fr) | ||
DE2713670A1 (de) | Aminochromanol-derivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneipraeparate | |
EP0722943A1 (fr) | 2-(2-n-Alkoxyphenyl)-purin-6-ones substitués en position 9 | |
EP0577040A2 (fr) | Procédé de préparation de l'ester tert.-butyle de l'acide (3R,5S)6-hydroxy-3,5-O-isopropylidène-3,5-dihydroxy-hexanoique | |
EP1140890B1 (fr) | Derives de chromane | |
WO1997025312A1 (fr) | NOUVEAUX DERIVES DE ROLIPRAM UTILISES COMME INHIBITEURS DE cAMP-PDE IV | |
EP0315009A2 (fr) | Dérivés de chromane, procédé pour leur préparation et leur utilisation dans les médicaments | |
CH639953A5 (en) | Process for the preparation of novel indolyloxymethyl-2-oxazolidinone derivatives and use thereof for the preparation of 1-amino-3-(indolyloxy)-2-propanol derivatives | |
DE3537075A1 (de) | Verfahren zur herstellung von clausenamid | |
EP0504351A1 (fr) | Procede pour la fabrication de 4-aryle-2-pyrrolidinones optiquement actifs | |
DE2426528A1 (de) | Verfahren zur herstellung von 25hydroxycholesterin | |
EP0414020B1 (fr) | Procédé pour la préparation de clausénamide et de néoclausénamide et leurs dérivés | |
DE3632589A1 (de) | Verfahren zur herstellung von (gamma)-butyrolactamen | |
EP0306649A1 (fr) | Acides 3,5-dihydroxycarboxyliques et leurs dérivés, leurs procédés de préparation, leur utilisation comme médicaments, préparations pharmaceutiques et produits intermédiaires | |
DE60306361T2 (de) | Verfahren zur herstellung von benazeprilhydrochlorid | |
DE69722565T2 (de) | Verfahren zur Herstellung von 4-Hydroxy-2-Pyrrolidinon und Verfahren zu deren Reinigung | |
EP0308785A2 (fr) | Ethers de dihydropyridines, leur procédés de préparation et leur utilisation | |
DE948974C (de) | Verfahren zur Herstellung von cyclischen 4-Halogenpregnan-3, 20-dion-3, 20-diketalen | |
DE4032054A1 (de) | Verfahren zur herstellung von optisch aktiven 4-aryl-2-pyrrolidinonen | |
DE4032059A1 (de) | Verfahren zur herstellung von optisch aktiven 4-aryl-2-pyrrolidinonen | |
DE3536956A1 (de) | Pyranderivate und ein verfahren zu ihrer herstellung | |
AT354656B (de) | Verfahren zur herstellung von hydroxy- cholesterinen |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
17P | Request for examination filed |
Effective date: 19920504 |
|
AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AT BE CH DE DK ES FR GB GR IT LI LU NL SE |
|
GRAG | Despatch of communication of intention to grant |
Free format text: ORIGINAL CODE: EPIDOS AGRA |
|
17Q | First examination report despatched |
Effective date: 19960201 |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION HAS BEEN WITHDRAWN |
|
18W | Application withdrawn |
Withdrawal date: 19960515 |