JP5501979B2 - 1−フルオロ−2−置換−3−クロロベンゼンの選択的脱プロトン化及び官能化の方法 - Google Patents
1−フルオロ−2−置換−3−クロロベンゼンの選択的脱プロトン化及び官能化の方法 Download PDFInfo
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- -1 1-fluoro-2-substituted-3-chlorobenzene Chemical class 0.000 title claims description 27
- 238000000034 method Methods 0.000 title claims description 14
- 230000005595 deprotonation Effects 0.000 title description 9
- 238000010537 deprotonation reaction Methods 0.000 title description 9
- 238000007306 functionalization reaction Methods 0.000 title description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 19
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical group [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims description 17
- 239000011541 reaction mixture Substances 0.000 claims description 14
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims description 13
- 239000012039 electrophile Substances 0.000 claims description 13
- 239000000203 mixture Substances 0.000 claims description 10
- 229910052744 lithium Inorganic materials 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- 239000003960 organic solvent Substances 0.000 claims description 6
- 229910002092 carbon dioxide Inorganic materials 0.000 claims description 5
- 239000001569 carbon dioxide Substances 0.000 claims description 5
- 150000002148 esters Chemical class 0.000 claims description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 claims description 3
- 150000008423 fluorobenzenes Chemical class 0.000 claims description 2
- 229930195733 hydrocarbon Natural products 0.000 claims description 2
- 239000004215 Carbon black (E152) Substances 0.000 claims 1
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 20
- 238000006243 chemical reaction Methods 0.000 description 15
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 239000010410 layer Substances 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 239000000523 sample Substances 0.000 description 6
- QASFEHCRPLPGES-UHFFFAOYSA-N 1-chloro-3-fluoro-2-methoxybenzene Chemical compound COC1=C(F)C=CC=C1Cl QASFEHCRPLPGES-UHFFFAOYSA-N 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- WRECIMRULFAWHA-UHFFFAOYSA-N trimethyl borate Chemical compound COB(OC)OC WRECIMRULFAWHA-UHFFFAOYSA-N 0.000 description 5
- 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 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical class CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 235000011089 carbon dioxide Nutrition 0.000 description 3
- 150000002170 ethers Chemical class 0.000 description 3
- 125000001153 fluoro group Chemical group F* 0.000 description 3
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 239000000376 reactant Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- ODAJPJWSLSBLLM-UHFFFAOYSA-N 4-chloro-2-fluoro-3-methoxybenzoic acid Chemical compound COC1=C(Cl)C=CC(C(O)=O)=C1F ODAJPJWSLSBLLM-UHFFFAOYSA-N 0.000 description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 2
- 239000012230 colorless oil Substances 0.000 description 2
- 229920001971 elastomer Polymers 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 239000004009 herbicide Substances 0.000 description 2
- 238000003760 magnetic stirring Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 238000010791 quenching Methods 0.000 description 2
- 230000000171 quenching effect Effects 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- DNIAPMSPPWPWGF-VKHMYHEASA-N (+)-propylene glycol Chemical compound C[C@H](O)CO DNIAPMSPPWPWGF-VKHMYHEASA-N 0.000 description 1
- YPFDHNVEDLHUCE-UHFFFAOYSA-N 1,3-propanediol Substances OCCCO YPFDHNVEDLHUCE-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- BHKKSKOHRFHHIN-MRVPVSSYSA-N 1-[[2-[(1R)-1-aminoethyl]-4-chlorophenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound N[C@H](C)C1=C(CN2C(NC(C3=C2C=CN3)=O)=S)C=CC(=C1)Cl BHKKSKOHRFHHIN-MRVPVSSYSA-N 0.000 description 1
- JIXDOBAQOWOUPA-UHFFFAOYSA-N 1-fluoro-2-methoxybenzene Chemical compound COC1=CC=CC=C1F JIXDOBAQOWOUPA-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
- LFDRRVSSSZUDJD-UHFFFAOYSA-N 4-chloro-2-fluoro-3-methoxybenzaldehyde Chemical compound COC1=C(Cl)C=CC(C=O)=C1F LFDRRVSSSZUDJD-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- WQOXQRCZOLPYPM-UHFFFAOYSA-N Dimethyl disulfide Natural products CSSC WQOXQRCZOLPYPM-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
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 150000001266 acyl halides Chemical class 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000012223 aqueous fraction Substances 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 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
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000003153 chemical reaction reagent Substances 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
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- JVSWJIKNEAIKJW-UHFFFAOYSA-N dimethyl-hexane Natural products CCCCCC(C)C JVSWJIKNEAIKJW-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- ZHNUHDYFZUAESO-UHFFFAOYSA-N formamide Substances NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 238000002955 isolation Methods 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
- 239000011777 magnesium Substances 0.000 description 1
- DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 239000011368 organic material Substances 0.000 description 1
- 229920000166 polytrimethylene carbonate Polymers 0.000 description 1
- ULWHHBHJGPPBCO-UHFFFAOYSA-N propane-1,1-diol Chemical compound CCC(O)O ULWHHBHJGPPBCO-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229920006395 saturated elastomer Polymers 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
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur 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
- 238000010792 warming Methods 0.000 description 1
- 239000002699 waste material Substances 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
- C07F1/00—Compounds containing elements of Groups 1 or 11 of the Periodic Table
- C07F1/02—Lithium compounds
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Description
(式中
Xは、F、OR1、又はNR2R3を表し、
Yは、H又はFを表し
R1、R2、及びR3は独立に、C1〜C4アルキル基を表す)
のリチオベンゼンの調製方法であって、
式II
(式中、X、Y、R1、R2、及びR3は前述の定義の通りである)
の置換フルオロベンゼンをアルキルリチウムと不活性有機溶媒中で接触させるステップを含む方法に関する。本発明の別の一態様では、リチオベンゼンを求電子試薬とさらに接触させる。好ましい求電子試薬としては、ボロン酸のエステル、二酸化炭素、N,N−ジアルキルホルムアミド、及びアルキルホルメートが挙げられる。
−70℃まで冷却した1リットル(L)の乾燥1,2−ジメトキシエタン(DME)中の2−クロロ−6−フルオロアニソール(100g)の溶液に、十分に磁気撹拌しながら、274ミリリットル(mL)のヘキサン中2.5M n−BuLiを12分(min)かけて加えた。添加中、反応物の温度が−58℃まで上昇した。ドライアイス浴を取り外し、反応物の温度を20分間で−50℃まで上昇させて、少量の白色固体を溶解させた。少量のサンプルを、0.15mLのMeSSMeを含有する1mLシリンジ中に直接抜き取った。このサンプルをエーテルで希釈し、水で抽出した。その有機相をGCによって検査した。この検査ではわずか4%しか出発物質が存在しなかった。
マグネチックスターラー、熱電対温度プローブを備えるサーモウェル、ゴム隔膜、及び窒素パッドを備える冷却器を取り付けた1リットルの3口フラスコ中で、無水1,2−ジメトキシエタン(313mL)中の2−クロロ−6−フルオロアニソール(40.2g)の溶液を調製した。ドライアイス/アセトン浴を使用して、この溶液を撹拌して−69.6℃まで冷却した。反応温度を−65℃未満に維持しながらシリンジポンプを使用して、ブチルリチウム溶液(115mLのヘキサン中2.5M ブチルリチウム)を4.15時間かけてゆっくり加えた。この反応混合物を−70.3℃〜−72.6℃で20分間撹拌した後、温度を−65℃未満に維持しながらシリンジポンプを使用して、トリメチルボレート(43mL)を1.6時間かけてゆっくり加えた。トリメチルボレートの添加終了後、反応混合物を周囲温度まで終夜ゆっくりと温めた。
マグネチックスターラー、熱電対温度プローブを備えるサーモウェル、ゴム隔膜、及び窒素パッドを備える冷却器を取り付けた100mLの3口フラスコ中で、無水1,2−ジメトキシエタン(75mL)中の2−クロロ−6−フルオロアニソール(9.6g)の溶液を調製した。ドライアイス/アセトン浴を使用し、この溶液を撹拌して−71.0℃まで冷却した。反応温度を−65℃未満に維持しながらシリンジポンプを使用して、ブチルリチウム溶液(31.5mLのヘキサン中2.5M ブチルリチウム)を1.57時間かけてゆっくりと加えた。反応混合物を−72.0℃〜−73.4℃で20分間撹拌した後、反応温度を−65℃未満に維持しながらシリンジポンプを使用して、トリメチルボレート(10.5mL)を43分かけてゆっくり加えた。トリメチルボレートの添加終了後、反応混合物を周囲温度まで終夜ゆっくりと温めた。
−70℃まで冷却され磁気撹拌される100mLの無水DME中の2−クロロ−6−フルオロアニソール(16.06g)の溶液に、反応温度を−55℃未満に維持しながら44mLのヘキサン中2.5M n−BuLiを30分かけて加えた。−70℃でさらに60分間反応物を撹拌した後、温度を−60℃未満に維持しながら乾燥二酸化炭素を反応混合物中に60分間バブリングした。室温まで温めた後、反応混合物を150mLのエーテルに加え、37%HCl水溶液で酸性化した。水層を2×150mLのエーテルで洗浄し、1つにまとめた有機層を飽和NaClで洗浄し、乾燥(Mg2SO4)させた。溶媒を除去すると、20.3gの白色固体が得られ、これをエーテル/ヘキサンから再結晶させて、16.4g(収率80%)の4−クロロ−2−フルオロ−3−メトキシ安息香酸を得た。MP 183−184°C;1H NMR(d6−DMSO,300 MHz)δ13.5(brs,1H),7.60(dd,1H,J=1.8,8.8 Hz),7.42(dd,1H,J=1.8,8.8 Hz),3.95(s,3 H).
−70℃まで冷却した2Lの乾燥テトラヒドロフラン(THF)中の2−クロロ−6−フルオロアニソール(321.2g)の溶液に、十分に磁気撹拌を行いながら、890mLのヘキサン中2.5M n−BuLiを30分かけて加えた。添加中、反応物の温度は−48〜−50℃に上昇し、添加終了後15分間その温度に維持した。溶液を−75℃まで冷却した後、温度を−50℃未満に維持しながら、100mLのTHF中の177gのジメチルホルムアミド(DMF)の溶液を加えた。反応物を室温まで温め、260gの37%HCl水溶液をゆっくりと加え、撹拌を2時間続けた。相を分離させ、その有機相を濃縮し、2Lのエーテル中に加えた。その溶液を500mLの10%HCl水溶液で2回洗浄した。得られた有機相をMgSO4上で乾燥させ、濾過し、濃縮して372gの薄い金色の油(GCにより純度93%)を得た。この油のバルブ・ツー・バルブ蒸留を行うと、282g(収率75%)の薄い金色の油が得られ、これを静置すると固化した。少量のサンプルをペンタンから結晶化させると、白色の細かい針状物質が得られた。MP 44−45°C;1H NMR(CDCl3,300 MHz)δ10.3(s,1H);7.5(dd,1H,J=6.6,8.5 Hz);7.3(m,1H);4.0(s,3H).
Claims (7)
- 式I
(式中、
Xは、F、OR1、又はNR2R3を表し、
Yは、H又はFを表し、
R1、R2、及びR3は独立に、C1〜C4アルキル基を表す)
のリチオベンゼンの調製方法であって、
式II
(式中、X、Y、R1、R2、及びR3は前述の定義の通りである)
の置換フルオロベンゼンをアルキルリチウムと不活性有機溶媒中で接触させるステップを
含む、方法。 - 前記アルキルリチウムがn−ブチルリチウムである、請求項1に記載の方法。
- 前記不活性有機溶媒が、炭化水素、エーテル、又はそれらの混合物である、請求項1に
記載の方法。 - XがOR1を表す、請求項1に記載の方法。
- 前記反応混合物を求電子試薬とさらに接触させる、請求項1に記載の方法。
- 前記求電子試薬が、ボロン酸エステル、二酸化炭素、N,N−ジアルキルホルムアミド、又はアルキルホルメートである、請求項5に記載の方法。
- 式
(式中、
Xは、OR1又はNR2R3を表し、
Yは、H又はFを表し、
Zは、−CO2Hを表し、
R1、R2、及びR3は独立に、C1〜C4アルキル基を表す)
の化合物。
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US10383465B2 (en) | 2012-04-12 | 2019-08-20 | Cabeau, Inc. | Travel pillow with lateral and rear support bar and a flat and thin back |
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CN101712603B (zh) * | 2009-12-04 | 2013-05-22 | 江苏工业学院 | 用格氏反应制备卤代甲基苯甲醛的方法 |
JP5790129B2 (ja) * | 2011-04-28 | 2015-10-07 | 東ソー株式会社 | 新規なナフタレン金属化合物及びその製造法 |
JP2012232924A (ja) * | 2011-04-28 | 2012-11-29 | Tosoh Corp | 新規なナフチルボロン酸化合物及びその製造法 |
DK2736912T3 (en) * | 2011-07-26 | 2018-09-17 | Dow Agrosciences Llc | PROCEDURES FOR INSULATING 4-CHLOR-2-FLUOR-3-SUBSTITUTED PHENYLBORONIC ACIDS |
CN103827124B (zh) * | 2011-09-14 | 2017-06-06 | 陶氏益农公司 | 用于形成硼酸类及其中间体的方法和系统 |
AU2012362364B2 (en) * | 2011-12-30 | 2017-06-29 | Corteva Agriscience Llc | Methods of isolating (4-chloro-2-fluoro-3-substituted-phenyl) boronates and methods of using the same |
KR102065543B1 (ko) * | 2011-12-30 | 2020-01-13 | 다우 아그로사이언시즈 엘엘씨 | 메틸 4-아미노-3-클로로-6-(4-클로로-2-플루오로-3-메톡시페닐)피리딘-2-카르복실레이트의 제조 방법 |
KR102062343B1 (ko) | 2011-12-30 | 2020-01-02 | 다우 아그로사이언시즈 엘엘씨 | 4-클로로-2-플루오로-3-치환된-페닐보론산 피나콜 에스테르의 형성 방법 및 그의 사용 방법 |
CN105072907A (zh) * | 2012-12-21 | 2015-11-18 | 美国陶氏益农公司 | 包含4-氨基-3-氯-6-(4-氯-2-氟-3-甲氧基苯基)吡啶-2-羧酸或其衍生物和呋草酮的除草组合物 |
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 |
CN106365978B (zh) * | 2016-08-31 | 2019-01-11 | 绍兴上虞华伦化工有限公司 | 一种2,3-二氟-6-甲氧基苯甲酸的制备方法 |
US20230174490A1 (en) | 2020-03-18 | 2023-06-08 | Corteva Agriscience Llc | Improved synthesis of 6-aryl-4-aminopicolinates |
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TWI287547B (en) * | 2000-06-14 | 2007-10-01 | Dow Agrosciences Llc | Process for the selective deprotonation and functionalization of 3-substituted benzotrifluorides |
DE10150615A1 (de) * | 2001-10-12 | 2003-04-30 | Clariant Gmbh | Verfahren zur metallorganischen Herstellung organischer Zwischenprodukte |
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JP4047040B2 (ja) * | 2002-03-14 | 2008-02-13 | 大日本インキ化学工業株式会社 | 2−フルオロ安息香酸誘導体の製造方法 |
DE10240261A1 (de) * | 2002-08-31 | 2004-03-11 | Clariant Gmbh | Verfahren zur metallorganischen Herstellung organischer Zwischenprodukte über Halogen-Metall-Austauschreaktionen |
DE10240262A1 (de) * | 2002-08-31 | 2004-03-11 | Clariant Gmbh | Verfahren zur metallorganischen Herstellung organischer Zwischenprodukte über Aryllithium-Basen |
PL1973881T3 (pl) * | 2006-01-13 | 2010-04-30 | Dow Agrosciences Llc | 6-(wielo-podstawione arylo)-4-aminopikoliniany i ich zastosowanie jako herbicydy |
CA2626018C (en) * | 2006-01-13 | 2014-05-06 | Dow Agrosciences Llc | 2-(poly-substituted aryl)-6-amino-5-halo-4-pyrimidinecarboxylic acids and their use as herbicides |
EP1878717A1 (en) * | 2006-07-14 | 2008-01-16 | Bayer Schering Pharma Aktiengesellschaft | Benzyl amines, a process for their production and their use as anti-inflammatory agents |
DE602008005319D1 (de) * | 2007-08-30 | 2011-04-14 | Dow Agrosciences Llc | 2-(substituierte phenyl)-6-amino-5-alkoxy-, thioalkoxy- und aminoalkyl-4-pyrimidincarboxylate und ihre verwendung als herbizide |
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US10383465B2 (en) | 2012-04-12 | 2019-08-20 | Cabeau, Inc. | Travel pillow with lateral and rear support bar and a flat and thin back |
US11129478B2 (en) | 2012-04-12 | 2021-09-28 | Cabeau, Inc. | Travel pillow |
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CN105254652A (zh) | 2016-01-20 |
BRPI0907417A2 (pt) | 2015-07-14 |
BRPI0907417B1 (pt) | 2017-06-20 |
ZA201004673B (en) | 2011-09-28 |
AU2009204153B2 (en) | 2013-08-01 |
EP2231678A1 (en) | 2010-09-29 |
PL2231678T3 (pl) | 2013-12-31 |
DK2231678T3 (da) | 2013-10-28 |
KR101599566B1 (ko) | 2016-03-03 |
CN101970446A (zh) | 2011-02-09 |
JP2011509300A (ja) | 2011-03-24 |
US7611647B2 (en) | 2009-11-03 |
IL206903A0 (en) | 2010-12-30 |
IL206903A (en) | 2017-06-29 |
WO2009089310A1 (en) | 2009-07-16 |
UA104282C2 (ru) | 2014-01-27 |
BRPI0907417B8 (pt) | 2022-06-28 |
EA020444B1 (ru) | 2014-11-28 |
KR20100114893A (ko) | 2010-10-26 |
ES2424981T3 (es) | 2013-10-10 |
TW200936549A (en) | 2009-09-01 |
CA2711308A1 (en) | 2009-07-16 |
AU2009204153A1 (en) | 2009-07-16 |
CA2711308C (en) | 2017-01-24 |
EA201070843A1 (ru) | 2011-02-28 |
EP2231678B1 (en) | 2013-07-24 |
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