DK2736912T3 - Fremgangsmåder til isolering af 4-chlor-2-fluor-3-substitueret phenylboronsyrer - Google Patents
Fremgangsmåder til isolering af 4-chlor-2-fluor-3-substitueret phenylboronsyrer Download PDFInfo
- Publication number
- DK2736912T3 DK2736912T3 DK12817070.1T DK12817070T DK2736912T3 DK 2736912 T3 DK2736912 T3 DK 2736912T3 DK 12817070 T DK12817070 T DK 12817070T DK 2736912 T3 DK2736912 T3 DK 2736912T3
- Authority
- DK
- Denmark
- Prior art keywords
- chloro
- fluoro
- acetonitrile
- phenylboronic acid
- water
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 27
- 239000002253 acid Substances 0.000 title description 6
- 150000007513 acids Chemical class 0.000 title description 2
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 159
- -1 4-chloro-2-fluoro-3-substituted phenylboronic acid Chemical class 0.000 claims description 103
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 71
- 150000003839 salts Chemical class 0.000 claims description 42
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims description 40
- 238000006243 chemical reaction Methods 0.000 claims description 39
- 239000000203 mixture Substances 0.000 claims description 39
- 239000000243 solution Substances 0.000 claims description 33
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 27
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 24
- 239000003960 organic solvent Substances 0.000 claims description 24
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 21
- GDJCQSNQOHRAGY-UHFFFAOYSA-N (4-chloro-2-fluoro-3-methoxyphenyl)boronic acid Chemical compound COC1=C(Cl)C=CC(B(O)O)=C1F GDJCQSNQOHRAGY-UHFFFAOYSA-N 0.000 claims description 15
- 239000007787 solid Substances 0.000 claims description 15
- 230000008569 process Effects 0.000 claims description 13
- 239000011780 sodium chloride Substances 0.000 claims description 9
- 230000015572 biosynthetic process Effects 0.000 claims description 7
- 238000001035 drying Methods 0.000 claims description 6
- 238000006069 Suzuki reaction reaction Methods 0.000 claims description 5
- 159000000000 sodium salts Chemical class 0.000 claims description 5
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims description 4
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 claims description 4
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 claims description 4
- 230000002194 synthesizing effect Effects 0.000 claims description 4
- DNIAPMSPPWPWGF-VKHMYHEASA-N (+)-propylene glycol Chemical compound C[C@H](O)CO DNIAPMSPPWPWGF-VKHMYHEASA-N 0.000 claims description 3
- YPFDHNVEDLHUCE-UHFFFAOYSA-N 1,3-propanediol Substances OCCCO YPFDHNVEDLHUCE-UHFFFAOYSA-N 0.000 claims description 3
- PSQMKVUSBRHKDG-UHFFFAOYSA-N 6-amino-2-(4-chloro-2-fluoro-3-methoxyphenyl)pyrimidine-4-carboxylic acid Chemical compound COC1=C(Cl)C=CC(C=2N=C(C=C(N)N=2)C(O)=O)=C1F PSQMKVUSBRHKDG-UHFFFAOYSA-N 0.000 claims description 3
- 229920000166 polytrimethylene carbonate Polymers 0.000 claims description 3
- 238000003786 synthesis reaction Methods 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- QASFEHCRPLPGES-UHFFFAOYSA-N 1-chloro-3-fluoro-2-methoxybenzene Chemical compound COC1=C(F)C=CC=C1Cl QASFEHCRPLPGES-UHFFFAOYSA-N 0.000 claims description 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 2
- 235000019270 ammonium chloride Nutrition 0.000 claims description 2
- 239000001110 calcium chloride Substances 0.000 claims description 2
- 229910001628 calcium chloride Inorganic materials 0.000 claims description 2
- 239000001103 potassium chloride Substances 0.000 claims description 2
- 235000011164 potassium chloride Nutrition 0.000 claims description 2
- OTYBMLCTZGSZBG-UHFFFAOYSA-L potassium sulfate Chemical compound [K+].[K+].[O-]S([O-])(=O)=O OTYBMLCTZGSZBG-UHFFFAOYSA-L 0.000 claims description 2
- 229910052939 potassium sulfate Inorganic materials 0.000 claims description 2
- 235000011151 potassium sulphates Nutrition 0.000 claims description 2
- 239000012047 saturated solution Substances 0.000 claims description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 claims description 2
- 235000011152 sodium sulphate Nutrition 0.000 claims description 2
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 claims 2
- 239000010410 layer Substances 0.000 description 61
- 239000011541 reaction mixture Substances 0.000 description 29
- WRECIMRULFAWHA-UHFFFAOYSA-N trimethyl borate Chemical compound COB(OC)OC WRECIMRULFAWHA-UHFFFAOYSA-N 0.000 description 19
- 239000003153 chemical reaction reagent Substances 0.000 description 18
- 239000012044 organic layer Substances 0.000 description 16
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 14
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 14
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 11
- 239000007795 chemical reaction product Substances 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- 235000011089 carbon dioxide Nutrition 0.000 description 7
- 229920006395 saturated elastomer Polymers 0.000 description 7
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 6
- 239000012266 salt solution Substances 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 5
- 238000002955 isolation Methods 0.000 description 5
- 239000011260 aqueous acid Substances 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 150000001642 boronic acid derivatives Chemical class 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 238000006138 lithiation reaction Methods 0.000 description 4
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
- 235000019341 magnesium sulphate Nutrition 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- 239000012267 brine Substances 0.000 description 3
- 239000012535 impurity Substances 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- SZCYTSLOMWQZRX-UHFFFAOYSA-N 4-amino-6-(4-chloro-2-fluoro-3-methoxyphenyl)pyridine-2-carboxylic acid Chemical class COC1=C(Cl)C=CC(C=2N=C(C=C(N)C=2)C(O)=O)=C1F SZCYTSLOMWQZRX-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000004009 herbicide Substances 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 238000005192 partition Methods 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 238000010977 unit operation Methods 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- ADGCCVYMKHWYGE-UHFFFAOYSA-N 2-(4-chloro-2-fluoro-3-methoxyphenyl)-1,3,2-dioxaborinane Chemical compound COC1=C(Cl)C=CC(B2OCCCO2)=C1F ADGCCVYMKHWYGE-UHFFFAOYSA-N 0.000 description 1
- 241000349731 Afzelia bipindensis Species 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 229910015446 B(OCH3)3 Inorganic materials 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- NHTMVDHEPJAVLT-UHFFFAOYSA-N Isooctane Chemical compound CC(C)CC(C)(C)C NHTMVDHEPJAVLT-UHFFFAOYSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical group [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000005595 deprotonation Effects 0.000 description 1
- 238000010537 deprotonation reaction Methods 0.000 description 1
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- JVSWJIKNEAIKJW-UHFFFAOYSA-N dimethyl-hexane Natural products CCCCCC(C)C JVSWJIKNEAIKJW-UHFFFAOYSA-N 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 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
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 description 1
- IHLVCKWPAMTVTG-UHFFFAOYSA-N lithium;carbanide Chemical compound [Li+].[CH3-] IHLVCKWPAMTVTG-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000005588 protonation Effects 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 238000009738 saturating Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000003385 sodium Chemical class 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 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
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
- C07F5/025—Boronic and borinic acid compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/38—Separation; Purification; Stabilisation; Use of additives
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Claims (15)
1. Fremgangsmåde til isolering af en 4-chlor-2-fluor-3-substitueret phenylboron-syre, hvilken fremgangsmåde omfatter: at bringe en blanding af vand, acetonitril og en 4-chlor-2-fluor-3-substitu-eret phenylboronsyre i kontakt med et salt for at danne et lag af et med vand blandbart organisk opløsningsmiddel og et vandlag; at opdele den 4-chlor-2-fluor-3-substituerede phenylboronsyre i laget af det med vand blandbare organiske opløsningsmiddel; og at adskille laget af det med vand blandbare organiske opløsningsmiddel der omfatter 4-chlor-2-fluor-3-substitueret phenylboronsyre, fra vandlaget.
2. Fremgangsmåden ifølge krav 1, hvorved kontakten af en blanding af vand, acetonitril og 4-chlor-2-fluor-3-substitueret phenylboronsyre med et salt omfatter at bringe en blanding af vand, acetonitril og en 4-chlor-2-fluor-3-methoxy-phenylboronsyre i kontakt med saltet.
3. Fremgangsmåden ifølge krav 1, hvorved: et salt tilsættes til en acetonitril/vandblanding der omfatter den 4-chlor-2-fluor-3-substituerede phenylboronsyre; den 4-chlor-2-fluor-3-substituerede phenylboronsyre fordeles ind i laget af acetonitril; og laget af acetonitril der omfatter den 4-chlor-2-fluor-3-substituerede phenylboronsyre, adskilles fra vandlaget.
4. Fremgangsmåden ifølge krav 3, hvorved tilsætning af et salt til en acetonitril/vandblanding der omfatter en 4-chlor-2-fluor-3-substitueret phenylboronsyre, omfatter at tilsætte et salt der er udvalgt fra gruppen, som består af natri-umchlorid, kaliumchlorid, calciumchlorid, natriumbromid, kaliumbromid, natriumsulfat, kaliumsulfat, ammoniumchlorid og kombinationer deraf, til acetonitril/vand-blandingen.
5. Fremgangsmåden ifølge krav 3, hvorved tilsætning af et salt til en aceto-nitril/vandblanding der omfatter en 4-chlor-2-fluor-3-substitueret phenylboron-syre, omfatter at tilsætte en mættet saltopløsning til acetonitril/vandblandingen, fortrinsvis en mættet natriumchloridopløsning.
6. Fremgangsmåden ifølge krav 3, hvorved tilsætning af et salt til en aceto-nitril/vandblanding der omfatter en 4-chlor-2-fluor-3-substitueret phenylboron-syre, omfatter at tilsætte et fast salt til acetonitril/vandblandingen, fortrinsvis fast natriumchlorid.
7. Fremgangsmåden ifølge krav 3 der yderligere omfatter at udvinde 4-chlor-2-fluor-3-substitueret phenylboronsyre fra laget af acetonitril.
8. Fremgangsmåde til syntetisering af 4-chlor-2-fluor-3-methoxy-phenylboron-syre, hvilken fremgangsmåde omfatter: at bringe 2-chlor-6-fluoranisol (2,6-CFA) i kontakt med n-butyllithium for at danne et lithieret derivat af 2,6-CFA; at bringe det lithierede derivat af 2,6-CFA i kontakt med B(OCH3)3 for at danne en boronsyreester af 2,6-CFA; at bringe boronsyreesteren af 2,6-CFA i at kontakt med vandigt natriumhydroxid for at danne et natriumsalt af boronsyren af 2,6-CFA; at bringe natriumsaltet af boronsyren af 2,6-CFA i kontakt med vandig saltsyre for at danne en opløsning af 4-chlor-2-fluor-3-methoxy-phenyl-boronsyre; at tilsætte acetonitril til opløsningen af 4-chlor-2-fluor-3-methoxy-phenyl-boronsyre for at danne en blanding af acetonitril, vand og 4-chlor-2-fluor- 3-methoxy-phenylboronsyre; at tilsætte et salt til blandingen af acetonitril, vand og 4-chlor-2-fluor-3-methoxy-phenylboronsyre for at danne et lag af acetonitril og et vandlag; og at adskille laget af acetonitril og vandlaget for at tilvejebringe en opløsning af 4-chlor-2-fluor-3-methoxy-phenylboronsyre i acetonitril.
9. Fremgangsmåden ifølge krav 8, hvorved tilsætning af et salt til blandingen af acetonitril, vand og 4-chlor-2-fluor-3-methoxyphenylboronsyre omfatter at tilsætte fast natriumchlorid til blandingen.
10. Fremgangsmåden ifølge krav 8, hvori tilsætning af et salt til blandingen af acetonitril, vand og 4-chlor-2-fluor-3-methoxy-phenylboronsyre omfatter at tilsætte en mættet opløsning af natriumchlorid til blandingen.
11. Fremgangsmåden ifølge krav 8 der yderligere omfatter at anvende opløsningen af 4-chlor-2-fluor-3-methoxy-phenylboronsyre i acetonitril til yderligere reaktioner uden koncentrering eller tørring, fortrinsvis at anvende opløsningen af 4-chlor-2-fluor-3-methoxy-phenylboronsyre i acetonitril i en Suzuki- koblingsreaktion uden koncentration eller tørring.
12. Fremgangsmåden ifølge krav 11, hvorved anvendelse af opløsningen af 4-chlor-2-fluor-3-methoxyphenylboronsyre i acetonitril til yderligere reaktioner uden koncentration eller tørring omfatter: at esterificere 4-chlor-2-fluor-3-methoxyphenylboronsyren i acetonitril med 1,3-propandiol for at fremstille (4-chlor-2-fluor-3-methoxyphenyl)-[1,3,2]-dioxabori-nan, som derpå anvendes som et mellemprodukt til en syntese af 6- (4-chlor-2-fluor-3-methoxyphenyl)-4-aminopicolinat eller 2-(4-chlor-2-fluor-3-methoxyphe-nyl)-6-amino-4 pyrimidincarboxylsyre.
13. Fremgangsmåde til anvendelse af 4-chlor-2-fluor-3-substitueret phenylboronsyre, hvilken fremgangsmåde omfatter: at tilsætte et salt til en acetonitril/vandblanding, der omfatter en 4-chlor- 2-fluor-3-substitueret phenylboronsyre; at opdele 4-chlor-2-fluor-3-substitueret phenylboronsyre i et lag af acetonitril; at adskille laget af acetonitril der omfatter 4-chlor-2-fluor-3-substitueret phenylboronsyre, fra et vandigt lag; og at anvende opløsningen af 4-chlor-2-fluor-3-substitueret phenylboronsyre i yderligere reaktioner uden koncentration eller tørring.
14. Fremgangsmåden ifølge krav 13, hvor 4-chlor-2-fluor-3-substitueret-phenyl-boronsyren har den følgende struktur:
hvor X er F, OR1 eller NR2R3; Y er H; og hver af Ri, R2 og R3 er uafhængigt en Ci-C4-alkylgruppe.
15. Fremgangsmåden ifølge krav 1 der yderligere omfatter at anvende opløsningen af 4-chlor-2-fluor-3-substitueret phenylboronsyre i acetonitril til en Suzuki-koblingsreaktion uden koncentration eller tørring.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161511867P | 2011-07-26 | 2011-07-26 | |
| PCT/US2012/048371 WO2013016557A2 (en) | 2011-07-26 | 2012-07-26 | Methods of isolating 4-chloro-2-fluoro-3-substituted-phenylboronic acids |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DK2736912T3 true DK2736912T3 (da) | 2018-09-17 |
Family
ID=47597753
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK12817070.1T DK2736912T3 (da) | 2011-07-26 | 2012-07-26 | Fremgangsmåder til isolering af 4-chlor-2-fluor-3-substitueret phenylboronsyrer |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US8822730B2 (da) |
| EP (1) | EP2736912B1 (da) |
| JP (2) | JP6491475B2 (da) |
| KR (1) | KR101995604B1 (da) |
| CN (1) | CN103814034B (da) |
| CA (1) | CA2842696C (da) |
| CO (1) | CO6890113A2 (da) |
| DK (1) | DK2736912T3 (da) |
| HK (1) | HK1200458A1 (da) |
| IL (1) | IL230623A (da) |
| MX (1) | MX338556B (da) |
| NZ (1) | NZ620043A (da) |
| PL (1) | PL2736912T3 (da) |
| RU (1) | RU2014106990A (da) |
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| KR101995604B1 (ko) * | 2011-07-26 | 2019-07-02 | 다우 아그로사이언시즈 엘엘씨 | ４-클로로-２-플루오로-３-치환된 페닐붕산의 단리 방법 |
| US8912339B2 (en) * | 2011-12-30 | 2014-12-16 | Dow Agrosciences, Llc. | Methods of forming 4-chloro-2-fluoro-3-substituted-phenylboronic acid pinacol esters and methods of using the same |
| WO2015035217A1 (en) * | 2013-09-05 | 2015-03-12 | Dow Agrosciences Llc | Methods for producing borylated arenes |
| TW201625354A (zh) | 2014-06-16 | 2016-07-16 | 陶氏農業科學公司 | 用於製備氧硼基化芳烴之方法 |
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| US4814521A (en) * | 1985-06-07 | 1989-03-21 | Kureha Kagaku Kogyo Kabushiki Kaisha | Process for producing 2,6-dihydroxynaphthalene and 2,6-diacetoxynaphthalene |
| KR100491163B1 (ko) | 2003-02-20 | 2005-05-24 | 대한민국 | 식품내 잔류농약 추출방법 |
| TWI355894B (en) | 2003-12-19 | 2012-01-11 | Du Pont | Herbicidal pyrimidines |
| US7300907B2 (en) | 2006-01-13 | 2007-11-27 | Dow Agrosciences Llc | 2-(Poly-substituted aryl)-6-amino-5-halo-4-pyrimidinecarboxylic acids and their use as herbicides |
| MY143535A (en) * | 2006-01-13 | 2011-05-31 | Dow Agrosciences Llc | 6-(poly-substituted aryl)-4-aminopicolinates and their use as herbicides |
| JP5209183B2 (ja) * | 2006-04-28 | 2013-06-12 | 東ソー・ファインケム株式会社 | 不純物の低減された２−シアノフェニルボロン酸又はそのエステル体の製造方法 |
| JP4998151B2 (ja) * | 2007-08-29 | 2012-08-15 | 株式会社ツムラ | 生薬試料中の残留農薬の精製方法 |
| ATE500230T1 (de) | 2007-08-30 | 2011-03-15 | Dow Agrosciences Llc | 2-(substituierte phenyl)-6-amino-5-alkoxy-, thioalkoxy- und aminoalkyl-4-pyrimidincarboxylate und ihre verwendung als herbizide |
| JP5444229B2 (ja) | 2007-10-02 | 2014-03-19 | ダウ アグロサイエンシィズ エルエルシー | ２−置換−６−アミノ−５−アルキル、アルケニル又はアルキニル−４−ピリミジンカルボン酸及び６−置換−４−アミノ−３−アルキル、アルケニル又はアルキニルピコリン酸並びに除草剤としてのそれらの使用 |
| HU230637B1 (hu) * | 2007-10-12 | 2017-05-29 | Egis Gyógyszergyár Nyilvánosan Működő Részvénytársaság | Eljárás rosuvastatin intermedierek előállítására |
| WO2009089310A1 (en) | 2008-01-11 | 2009-07-16 | Dow Agrosciences Llc | Process for the selective deprotonation and functionalization of 1-fluoro-2-substituted-3-chlorobenzenes |
| KR101995604B1 (ko) * | 2011-07-26 | 2019-07-02 | 다우 아그로사이언시즈 엘엘씨 | ４-클로로-２-플루오로-３-치환된 페닐붕산의 단리 방법 |
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Also Published As
| Publication number | Publication date |
|---|---|
| CA2842696A1 (en) | 2013-01-31 |
| JP2017122088A (ja) | 2017-07-13 |
| KR101995604B1 (ko) | 2019-07-02 |
| IL230623A (en) | 2016-09-29 |
| CO6890113A2 (es) | 2014-03-10 |
| WO2013016557A3 (en) | 2013-06-13 |
| PL2736912T3 (pl) | 2018-11-30 |
| MX2014001009A (es) | 2014-05-13 |
| EP2736912B1 (en) | 2018-06-13 |
| CN103814034A (zh) | 2014-05-21 |
| TR201810920T4 (tr) | 2018-08-27 |
| EP2736912A2 (en) | 2014-06-04 |
| NZ620043A (en) | 2016-02-26 |
| RU2014106990A (ru) | 2015-09-10 |
| JP2014524933A (ja) | 2014-09-25 |
| US20130030213A1 (en) | 2013-01-31 |
| JP6505756B2 (ja) | 2019-04-24 |
| EP2736912A4 (en) | 2015-03-04 |
| IL230623A0 (en) | 2014-03-31 |
| WO2013016557A2 (en) | 2013-01-31 |
| US8822730B2 (en) | 2014-09-02 |
| JP6491475B2 (ja) | 2019-03-27 |
| HK1200458A1 (en) | 2015-08-07 |
| MX338556B (es) | 2016-04-21 |
| KR20140050071A (ko) | 2014-04-28 |
| CA2842696C (en) | 2019-09-10 |
| CN103814034B (zh) | 2017-02-15 |
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