GB2155471A - Method for the preparation of an isoxazole derivative - Google Patents
Method for the preparation of an isoxazole derivative Download PDFInfo
- Publication number
- GB2155471A GB2155471A GB08505893A GB8505893A GB2155471A GB 2155471 A GB2155471 A GB 2155471A GB 08505893 A GB08505893 A GB 08505893A GB 8505893 A GB8505893 A GB 8505893A GB 2155471 A GB2155471 A GB 2155471A
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- United Kingdom
- Prior art keywords
- formula
- compound
- alkyl group
- carbon atoms
- stands
- 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.)
- Granted
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 9
- 150000002545 isoxazoles Chemical class 0.000 title claims abstract description 5
- 238000000034 method Methods 0.000 title claims description 15
- 150000001875 compounds Chemical class 0.000 claims abstract description 28
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 claims abstract description 12
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 9
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000002253 acid Substances 0.000 claims abstract description 7
- 239000007800 oxidant agent Substances 0.000 claims abstract description 6
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 4
- 150000002367 halogens Chemical class 0.000 claims abstract description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 4
- 230000003301 hydrolyzing effect Effects 0.000 claims abstract description 3
- 230000007062 hydrolysis Effects 0.000 claims description 6
- 238000006460 hydrolysis reaction Methods 0.000 claims description 6
- WKDDRNSBRWANNC-ATRFCDNQSA-N Thienamycin Chemical compound C1C(SCCN)=C(C(O)=O)N2C(=O)[C@H]([C@H](O)C)[C@H]21 WKDDRNSBRWANNC-ATRFCDNQSA-N 0.000 abstract description 6
- WKDDRNSBRWANNC-UHFFFAOYSA-N Thienamycin Natural products C1C(SCCN)=C(C(O)=O)N2C(=O)C(C(O)C)C21 WKDDRNSBRWANNC-UHFFFAOYSA-N 0.000 abstract description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- PSQVMDJYCMIYNH-UHFFFAOYSA-N 2-(4-methoxycarbonyl-5-methyl-1,2-oxazol-3-yl)acetic acid Chemical compound COC(=O)C1=C(C)ON=C1CC(O)=O PSQVMDJYCMIYNH-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- UPVVZCLEAHDZFZ-UHFFFAOYSA-N 3-(carboxymethyl)-5-methyl-1,2-oxazole-4-carboxylic acid Chemical compound CC=1ON=C(CC(O)=O)C=1C(O)=O UPVVZCLEAHDZFZ-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- -1 ethyl 5-methyl-4-methoxycarbonylisoxazole-3-yl-acetate Chemical compound 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 235000015497 potassium bicarbonate Nutrition 0.000 description 2
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 2
- 239000011736 potassium bicarbonate Substances 0.000 description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- QWPPOHNGKGFGJK-UHFFFAOYSA-N hypochlorous acid Chemical compound ClO QWPPOHNGKGFGJK-UHFFFAOYSA-N 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000004289 sodium hydrogen sulphite Substances 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/10—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members 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
- C07D261/18—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Abstract
The isoxazole derivative of formula (I> <IMAGE> may be prepared by treating a compound of formula (II> <IMAGE> wherein R<1> stands for an alkyl group containing 1 to 6 carbon atoms, with an oxidizing agent, such as manganese dioxide, potassium iodide and halogen or a hypohalic acid, hydrolizing the resulting compound of formula (II> <IMAGE> wherein R stands for a hydrogen atom or an alkyl group containing 1 to 6 carbon atoms, and recovering the product obtained in a manner known per se. Compound (I) is an intermediate for the preparation of thienamycin.
Description
SPECIFICATION
Method for the preparation of an isoxazole derivative
The present invention relates to a new method for the preparation of the isoxazole derivative of the formula
The compound of the formula (I) is known from the Hungarian patent application No.
661/83 of the Applicant as an intermediate for the preparation of thienamycin.
It has been found that the compound of the formula (I) can be prepared from a compound of the formula
in a very simple manner.
The compounds of the formula (III), wherein R1 stands for an alkyl group containing 1 to 6 carbon atoms, are known from the U.S. patent specification No. 4,269,772 as intermediates for the preparation of thienamycin. However, according to our experiments the thienamycin synthesis in which compounds of the formula (III) are subjected to the reduction method disclosed in said U.S. patent specification is practically inoperative.As it will be disclosed in
Examples 5 and 6 of the present specification, a compound of the formula (I) prepared from a compound of the formula (III) can be converted into a compound of the formula
wherein R1 stands for an alkyl group containing 1 to 6 carbon atoms, and this latter compound can subsequently be converted into the formula
which is the key intermediate for the preparation of thienamycin. The compound of the formula (V) can be converted into thienamycin according to the method described in the European patent application No. 32,400.
Thus, the invention relates to a method for the preparation of the compound of the formula
This method is characterized by treating a compound of the formula
wherein R1 stands for an alkyl group containing 1 to 6 carbon atoms, with a suitable oxidizing agent, hydrolizing the resulting compound of the formula
wherein R stands for a hydrogen atom or an alkyl group containing 1 to 6 carbon atoms, and recovering the product obtained in a manner known per se.
The first step of the method according to the invention is the oxidation of a compound of the formula (III). As oxidizing agent an aqueous solution containing potassium iodide and a halogen, e.g. iodine, bromine or chlorine, is used or said halogen can be replaced by a hypohaloic acid, mainly hypochlorous acid. A compound of the formula (III) is subjected to oxidation in a reaction-inert organic solvent at elevated temperature, suitably at reflux temperature. During this reaction a compound of the formula (II), wherein R is a hydrogen atom, is formed. This compound is recovered through extraction and then subjected to hydrolysis, yielding the compound of the formula (I).
As oxidising agent manganese dioxide can also be used, suitably in an active form. This type of oxidation is carried out in a reaction-inert organic solvent and in the reaction a compound of the formula (II), wherein R is an alkyl group containing 1 to 6 carbon atoms is obtained. This compound is, if desired, recovered and then subjected to hydrolysis. However, it is more preferable to subject a compound of the formula (II) to direct hydrolysis.
In both cases the hydrolysis is promoted suitably with an acid, although a base can be used as well. In the latter case the yield is less.
The hydrolysis product can be recovered through evaporation of the solvent.
The invention is elucidated by the aid of the following non-limiting Examples.
Example 1 5-Methyl-4-methoxycarbonylisoxazole-3-yl-acetic acid
To a solution of 229 g. (10 mmoles) of ethyl trans5-methyl-4-methoxycarbonyl-4,5-dihydroi- soxazole-3-yl-acetate in 7.5 ml. of tetrahydrofuran a solution of 5.68 g. (34 mmoles) of potassium iodide and 2.68 9. (10.5 mmoles) of iodine in 25 ml. of water is added and the reaction mixture is refluxed for 6 hours under stirring. The excess of iodine is destroyed through the addition of sodium bisulphite and the mixture is subjected to a fivefold extraction with 10 ml. of dichloromethane, each. The combined organic phases are washed twice with 10 ml. of saturated sodium chloride solution, each, then dried over magnesium sulphate, filtered and evaporated. The residue is crystallized by triturating with ether.
Yield: 1.56 g. (79%)
M.p.: 135"C IR (KBr): 3500-2400, 1730 (broad), 1710, 1600 cm-'.
tH-NMR (CDCl3), 6 = 2.63 (3H), 3,76 s (3H), 3.88 s (2H), 10.10 s (1 H).
Example 2 4-Carboxy-5-methylisoxazole-3-yl-acetic acid
1.99 9. (10 mmoles) of 5-methyl-4-methoxycarbonylisoxazole-3-yl-acetic acid prepared according to the method of Example 1, is emulsified in a mixture of 10 ml. of water and 10 ml. of concentrated hydrochlorid acid and refluxed for two hours. The solution obtained is clarified in a hot state, then filtered and the filtrate is concentrated to a half of its original volume. The concentrate is cooled, the crystals obtained are filtered and dried.
Yield: 1.78 g. (96%)
IR (KBr): 3600-2400, 1720, 1690, 1610cm-1.
'H-NMR (D20): 8 2.55 s (3H), 3.85 s (2H).
H-NMR tDMSO-d6): 8 2.4 s (3H), 3.55 s (2H).
Example 3
Ethyl 5-methyl-4-methoxycarbonylisoxazo le-3-yI-acetate A mixture of 3 g. of ethyl trnns5-methyl-4-methoxycarbonyl-4,5-dihydroisoxazole-3-yI-acetate and 1 5 g. of active manganese dioxide in 100 ml. of dry benzene is refluxed for 6 hours. The water splitting off in the reaction is removed continuously by azeotropic destillation. After the termination of the reaction the reaction mixture is filtered and the filtrate is evaporated to dryness under reduced pressure.
Yield: 1.8 g. (60%) B.p.: 11 5"C/0.2 mm Hg
IR (film): 1715, 1725cm-1.
H-NMR (CDCI3): 81.25 t (3H), 2.65 s (3H), 3.80 s (3H)
3.85 s (2H), 4.15 q (2H).
Example 4 5-Methyl-4-methoxycarbonylisoxazole-3-yl-acetic acid
A mixture of 0.5 g. of ethyl 5-methyl-4-methoxycarbonylisoxazole-3-yl-acetate prepared according to the method of Example 3 and 3 ml. of a 20% aqueous hydrochlorid acid solution is refluxed for 30 minutes, then the reaction mixture is evaporated and the residue is crystallized through triturating with ether.
Yield: 0.4 g. (90%)
The physical constants of this compound are identical with those of the product of Example 1.
Example 5 Butyl 5-methyl-4-mbutoxycarbonyl isozaxole-3-yl-acetate 1 3 g. (70.2 mmoles) of 4-carboxy-5-methylisoxazole-3-yl-acetic acid prepared according to the method of Example 2 are refluxed in a mixture of 60 ml. of nbutanol, 1 50 ml. of benzene and 1 5 ml. of concentrated sulphuric acid for 16 hours under a reflux condenser fitted with a waterseparating equipment, then the reaction mixture is added to ice. The phases are separated nd the aqueous phase is extracted twice with 75 ml. of benzene, each. The combined organic phases are washed in sequence twice with 100 ml. of water, each, twice with 75 ml. of a 5% aqueous solution of sodium bicarbonate, each and finally twice with 75 ml. of water, each.The organic phase is dried over calcium chloride and evaporated under reduced pressure. 23 g. of oily residue is obtained which can be used in the next reaction step without further purification.
If desired, it can be purified by vacuum destillation (b.p.: 130-131 C/0.1 mm Hg).
Example 6 /2 RS, 3 us, 4SR /-4-benzylamino-2-methyl-6-oxotetrahydropiran-3-yI-carboxylic acid hydrochloride
4 g. (13.3 mmoles) of butyl 5-methyl-4- > butoxycarbonylisoxazole-3-yl-acetate in 40 ml. of 99.5% glacial acetic acid is hydrogenated in the presence of 0.5 g. of a 10% palladium-oncharcoal catalyst at atmospheric pressure and room temperature. After the calculated amount of hydrogen has been absorbed, the catalyst is removed by filtration and to the filtrate 1.93 g. (27 mmoles) of sodium cyanotrihydroborate is added under stirring within 20 minutes. The reaction mixture is stirred at room temperature for 3 hours, then over a water bath of 80"C for additional 10 minutes.The reaction mixture is allowed to cool to room temperature, treated with 1.6 ml.
(16.5 mmoles) of benzaldehyde and allowed to stand overnight. The reaction mixture is then treated with a further 1.4 g. amount (20 mmoles) of sodium cyanotrihydroborate under stirring within 20 minutes and allowed to stand for 24 hours.
The solution so obtained is evaporated in vacuo and from the residue 50 ml. of nheptane is distilled off. The residue is treated with 50 ml. of ether, then dropwise 40 ml. of a 10% aqueous solution of potassium bicarbonate are added under stirring. The ethereal phase is separated and the aqueous phase is extracted twice with 40 ml. of ether, each. The combined ethereal phases are washed first with 40 ml., then with 20 ml. of a 10% aqueous potassium bicarbonate solution, and finally twice with 20 ml. of a saturated aqueous sodium chloride solution, each. The organic phase is evaporated to dryness, the residue is refluxed in 30 ml. of concentrated aqueous hydrochloric acid solution for 3 hours, allowed to cool to room temperature, washed twice with 30 ml. of ether, each and evaporated.
The solid residue is triturated with 20 ml. of acetone, the crystals obtained are filtered off, washed once with 10 ml. of acetone, twice with 10 ml. of ether, each and finally with 10 ml. of water, and dried.
Yield: 2.1 g. (52%)
M.p.: 163-164C.
Claims (4)
1. A method for the preparation of the isoxazole derivative of the formula
characterized by treating a compound of the formula
wherein R1 stands for an alkyl group containing 1 to 6 carbon atoms, with a suitable oxidizing agent, hydrolizing the resulting compound of the formula
wherein R stands for a hydrogen atom or an alkyl group containing 1 to 6 carbon atoms, and recovering the product obtained in a manner known per se.
2. The method as claimed in claim 1 characterized by using manganese dioxide or an aqueous solutuion containing potassium iodide and a halogen or a hypohaloic acid as oxidizing agent.
3. The method as claimed in claim 1 characterized by carrying out the hydrolysis in the presence of an acid.
4. The compound of the formula
whenever prepared by a process according to any of claims 1 to 3.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU93984A HU191592B (en) | 1984-03-09 | 1984-03-09 | Process for preparing isoxazole-derivatives |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| GB8505893D0 GB8505893D0 (en) | 1985-04-11 |
| GB2155471A true GB2155471A (en) | 1985-09-25 |
| GB2155471B GB2155471B (en) | 1987-10-21 |
Family
ID=10952126
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB08505893A Expired GB2155471B (en) | 1984-03-09 | 1985-03-07 | Method for the preparation of an isoxazole derivative |
Country Status (7)
| Country | Link |
|---|---|
| JP (1) | JPS60204772A (en) |
| BE (1) | BE901899A (en) |
| ES (1) | ES8602708A1 (en) |
| FR (1) | FR2560875B1 (en) |
| GB (1) | GB2155471B (en) |
| HU (1) | HU191592B (en) |
| PT (1) | PT80071B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5473069A (en) * | 1990-03-21 | 1995-12-05 | Basf Aktiengesellschaft | Preparation of isoxazole-4,5-dicarboxylic diesters |
-
1984
- 1984-03-09 HU HU93984A patent/HU191592B/en not_active IP Right Cessation
-
1985
- 1985-03-07 FR FR8503353A patent/FR2560875B1/en not_active Expired
- 1985-03-07 PT PT8007185A patent/PT80071B/en unknown
- 1985-03-07 JP JP4383385A patent/JPS60204772A/en active Pending
- 1985-03-07 GB GB08505893A patent/GB2155471B/en not_active Expired
- 1985-03-08 BE BE0/214619A patent/BE901899A/en not_active IP Right Cessation
- 1985-03-08 ES ES541101A patent/ES8602708A1/en not_active Expired
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5473069A (en) * | 1990-03-21 | 1995-12-05 | Basf Aktiengesellschaft | Preparation of isoxazole-4,5-dicarboxylic diesters |
Also Published As
| Publication number | Publication date |
|---|---|
| BE901899A (en) | 1985-09-09 |
| GB2155471B (en) | 1987-10-21 |
| FR2560875A1 (en) | 1985-09-13 |
| GB8505893D0 (en) | 1985-04-11 |
| PT80071A (en) | 1985-04-01 |
| HU191592B (en) | 1987-03-30 |
| PT80071B (en) | 1986-11-24 |
| ES541101A0 (en) | 1985-12-01 |
| ES8602708A1 (en) | 1985-12-01 |
| FR2560875B1 (en) | 1988-02-12 |
| JPS60204772A (en) | 1985-10-16 |
| HUT37927A (en) | 1986-03-28 |
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