JP2019172659A - 含フッ素アルキン化合物及びその製造方法、並びに製造用中間体 - Google Patents
含フッ素アルキン化合物及びその製造方法、並びに製造用中間体 Download PDFInfo
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- JP2019172659A JP2019172659A JP2019044878A JP2019044878A JP2019172659A JP 2019172659 A JP2019172659 A JP 2019172659A JP 2019044878 A JP2019044878 A JP 2019044878A JP 2019044878 A JP2019044878 A JP 2019044878A JP 2019172659 A JP2019172659 A JP 2019172659A
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- compound
- fluorine
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- -1 alkyne compound Chemical class 0.000 title claims abstract description 98
- 229910052731 fluorine Inorganic materials 0.000 title claims abstract description 88
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 title claims abstract description 73
- 239000011737 fluorine Substances 0.000 title claims abstract description 73
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 25
- 150000001875 compounds Chemical class 0.000 claims abstract description 91
- 150000007514 bases Chemical class 0.000 claims abstract description 64
- 229940126062 Compound A Drugs 0.000 claims description 28
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 claims description 28
- 125000001153 fluoro group Chemical group F* 0.000 claims description 18
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 14
- 229910052794 bromium Inorganic materials 0.000 claims description 14
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 13
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 9
- 229910052783 alkali metal Inorganic materials 0.000 claims description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- 229920002554 vinyl polymer Polymers 0.000 claims description 6
- 125000001246 bromo group Chemical group Br* 0.000 claims description 5
- 239000000460 chlorine Chemical group 0.000 claims description 5
- 229910052801 chlorine Chemical group 0.000 claims description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- 229910000102 alkali metal hydride Inorganic materials 0.000 claims description 3
- 150000008046 alkali metal hydrides Chemical class 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 15
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 abstract description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 63
- 239000000126 substance Substances 0.000 description 55
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 34
- 238000005481 NMR spectroscopy Methods 0.000 description 33
- 239000000243 solution Substances 0.000 description 31
- 238000006243 chemical reaction Methods 0.000 description 28
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 24
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
- 238000004458 analytical method Methods 0.000 description 21
- 125000004432 carbon atom Chemical group C* 0.000 description 18
- 239000002904 solvent Substances 0.000 description 16
- 230000015572 biosynthetic process Effects 0.000 description 13
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- 239000000203 mixture Substances 0.000 description 12
- 238000003786 synthesis reaction Methods 0.000 description 12
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 11
- 239000012044 organic layer Substances 0.000 description 11
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 11
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 10
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- JILAKKYYZPDQBE-UHFFFAOYSA-N 1,1,2,2,3,3,4,4-octafluoro-1,4-diiodobutane Chemical compound FC(F)(I)C(F)(F)C(F)(F)C(F)(F)I JILAKKYYZPDQBE-UHFFFAOYSA-N 0.000 description 8
- RHWQIEGGACEYLL-UHFFFAOYSA-N 3,3,4,4,5,5,6,6-octafluoroocta-1,7-diyne Chemical compound FC(C#C)(C(C(C(C#C)(F)F)(F)F)(F)F)F RHWQIEGGACEYLL-UHFFFAOYSA-N 0.000 description 8
- KJHISUDZYOEWNG-UHFFFAOYSA-N 3,3,4,4-tetrafluorohexa-1,5-diyne Chemical compound C#CC(C(C#C)(F)F)(F)F KJHISUDZYOEWNG-UHFFFAOYSA-N 0.000 description 8
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 8
- 235000019341 magnesium sulphate Nutrition 0.000 description 8
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 7
- 150000004820 halides Chemical group 0.000 description 7
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 7
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 6
- 0 C*(C)C(CI)BrC Chemical compound C*(C)C(CI)BrC 0.000 description 6
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 6
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 6
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 6
- ZDWYFWIBTZJGOR-UHFFFAOYSA-N bis(trimethylsilyl)acetylene Chemical group C[Si](C)(C)C#C[Si](C)(C)C ZDWYFWIBTZJGOR-UHFFFAOYSA-N 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 6
- 230000003197 catalytic effect Effects 0.000 description 5
- 229940126214 compound 3 Drugs 0.000 description 5
- 239000012299 nitrogen atmosphere Substances 0.000 description 5
- 238000007342 radical addition reaction Methods 0.000 description 5
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 4
- NZXVPCQHQVWOFD-UHFFFAOYSA-N 1,1,2,2-tetrafluoro-1,2-diiodoethane Chemical compound FC(F)(I)C(F)(F)I NZXVPCQHQVWOFD-UHFFFAOYSA-N 0.000 description 4
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 4
- WADSJYLPJPTMLN-UHFFFAOYSA-N 3-(cycloundecen-1-yl)-1,2-diazacycloundec-2-ene Chemical compound C1CCCCCCCCC=C1C1=NNCCCCCCCC1 WADSJYLPJPTMLN-UHFFFAOYSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 4
- LFZAGIJXANFPFN-UHFFFAOYSA-N N-[3-[4-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)piperidin-1-yl]-1-thiophen-2-ylpropyl]acetamide Chemical compound C(C)(C)C1=NN=C(N1C1CCN(CC1)CCC(C=1SC=CC=1)NC(C)=O)C LFZAGIJXANFPFN-UHFFFAOYSA-N 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 4
- 239000012300 argon atmosphere Substances 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 229940125773 compound 10 Drugs 0.000 description 4
- 229940125797 compound 12 Drugs 0.000 description 4
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 4
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 4
- 230000002194 synthesizing effect Effects 0.000 description 4
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 3
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 3
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 3
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 3
- 229940126657 Compound 17 Drugs 0.000 description 3
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 125000002355 alkine group Chemical group 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 229940126142 compound 16 Drugs 0.000 description 3
- 238000006704 dehydrohalogenation reaction Methods 0.000 description 3
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 238000004817 gas chromatography Methods 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- LZWQNOHZMQIFBX-UHFFFAOYSA-N lithium;2-methylpropan-2-olate Chemical compound [Li+].CC(C)(C)[O-] LZWQNOHZMQIFBX-UHFFFAOYSA-N 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 3
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- YFNKIDBQEZZDLK-UHFFFAOYSA-N triglyme Chemical compound COCCOCCOCCOC YFNKIDBQEZZDLK-UHFFFAOYSA-N 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 239000008096 xylene Substances 0.000 description 3
- GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 description 2
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 2
- IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 description 2
- LZDKZFUFMNSQCJ-UHFFFAOYSA-N 1,2-diethoxyethane Chemical compound CCOCCOCC LZDKZFUFMNSQCJ-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- AMGOALNXHWUMGS-UHFFFAOYSA-N 3,3,4,4,5,5,6,6,7,7,8,8-dodecafluorodeca-1,9-diyne Chemical compound C#CC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C#C AMGOALNXHWUMGS-UHFFFAOYSA-N 0.000 description 2
- QDFXRVAOBHEBGJ-UHFFFAOYSA-N 3-(cyclononen-1-yl)-4,5,6,7,8,9-hexahydro-1h-diazonine Chemical compound C1CCCCCCC=C1C1=NNCCCCCC1 QDFXRVAOBHEBGJ-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- 239000003905 agrochemical Substances 0.000 description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 2
- 125000002009 alkene group Chemical group 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000012230 colorless oil Substances 0.000 description 2
- 229940125904 compound 1 Drugs 0.000 description 2
- 229940126543 compound 14 Drugs 0.000 description 2
- 229940125758 compound 15 Drugs 0.000 description 2
- 229940125782 compound 2 Drugs 0.000 description 2
- 229940125810 compound 20 Drugs 0.000 description 2
- 229940125898 compound 5 Drugs 0.000 description 2
- LSXWFXONGKSEMY-UHFFFAOYSA-N di-tert-butyl peroxide Chemical compound CC(C)(C)OOC(C)(C)C LSXWFXONGKSEMY-UHFFFAOYSA-N 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 150000002221 fluorine Chemical class 0.000 description 2
- JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 description 2
- 230000002140 halogenating effect Effects 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 2
- 229910000103 lithium hydride Inorganic materials 0.000 description 2
- ANYSGBYRTLOUPO-UHFFFAOYSA-N lithium tetramethylpiperidide Chemical compound [Li]N1C(C)(C)CCCC1(C)C ANYSGBYRTLOUPO-UHFFFAOYSA-N 0.000 description 2
- 239000008204 material by function Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- SKTCDJAMAYNROS-UHFFFAOYSA-N methoxycyclopentane Chemical compound COC1CCCC1 SKTCDJAMAYNROS-UHFFFAOYSA-N 0.000 description 2
- IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 2
- 229910000105 potassium hydride Inorganic materials 0.000 description 2
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000009257 reactivity Effects 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- MOEPRDRGTVPGHW-UHFFFAOYSA-N 1,1,1,2,2,3,4,4-octafluoro-3,4-diiodobutane Chemical compound FC(F)(F)C(F)(F)C(F)(I)C(F)(F)I MOEPRDRGTVPGHW-UHFFFAOYSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- CPEUTDCQXYVUEP-UHFFFAOYSA-N 2,9-dibromo-3,3,4,4,5,5,6,6,7,7,8,8-dodecafluorodeca-1,9-diene Chemical compound BrC(=C)C(C(C(C(C(C(C(=C)Br)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F CPEUTDCQXYVUEP-UHFFFAOYSA-N 0.000 description 1
- XKBHBVFIWWDGQX-UHFFFAOYSA-N 2-bromo-3,3,4,4,5,5,5-heptafluoropent-1-ene Chemical compound FC(F)(F)C(F)(F)C(F)(F)C(Br)=C XKBHBVFIWWDGQX-UHFFFAOYSA-N 0.000 description 1
- KSQRGPQLCIXCCL-UHFFFAOYSA-N 2-bromo-3,3,4,4,5,5,6,6,6-nonafluorohex-1-ene Chemical compound FC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(Br)=C KSQRGPQLCIXCCL-UHFFFAOYSA-N 0.000 description 1
- KSXRFZHNNOXBLE-UHFFFAOYSA-N 2-bromo-3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooct-1-ene Chemical compound FC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(Br)=C KSXRFZHNNOXBLE-UHFFFAOYSA-N 0.000 description 1
- FISQXYDFCVEFII-UHFFFAOYSA-N 2-chloro-3,3,4,4,5,5,5-heptafluoropent-1-ene Chemical compound FC(F)(F)C(F)(F)C(F)(F)C(Cl)=C FISQXYDFCVEFII-UHFFFAOYSA-N 0.000 description 1
- CVDYYPTVATXTLA-UHFFFAOYSA-N 2-chloro-3,3,4,4,5,5,6,6,6-nonafluorohex-1-ene Chemical compound FC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(Cl)=C CVDYYPTVATXTLA-UHFFFAOYSA-N 0.000 description 1
- LQAPOTKKMIZDGP-UHFFFAOYSA-N 3,3,4,4,5,5,5-heptafluoropent-1-ene Chemical compound FC(F)(F)C(F)(F)C(F)(F)C=C LQAPOTKKMIZDGP-UHFFFAOYSA-N 0.000 description 1
- GQXURUTWTUSYPE-UHFFFAOYSA-N 3,3,4,4,5,5,5-heptafluoropent-1-yne Chemical compound FC(F)(F)C(F)(F)C(F)(F)C#C GQXURUTWTUSYPE-UHFFFAOYSA-N 0.000 description 1
- GVEUEBXMTMZVSD-UHFFFAOYSA-N 3,3,4,4,5,5,6,6,6-nonafluorohex-1-ene Chemical compound FC(F)(F)C(F)(F)C(F)(F)C(F)(F)C=C GVEUEBXMTMZVSD-UHFFFAOYSA-N 0.000 description 1
- BVDUDNZLDHKIJQ-UHFFFAOYSA-N 3,3,4,4,5,5,6,6,6-nonafluorohex-1-yne Chemical compound FC(F)(F)C(F)(F)C(F)(F)C(F)(F)C#C BVDUDNZLDHKIJQ-UHFFFAOYSA-N 0.000 description 1
- QAFBNSWDAGQWLF-UHFFFAOYSA-N 3,3,4,4,5,5,6,6,7,7,7-undecafluorohept-1-ene Chemical compound FC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C=C QAFBNSWDAGQWLF-UHFFFAOYSA-N 0.000 description 1
- FYQFWFHDPNXORA-UHFFFAOYSA-N 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooct-1-ene Chemical compound FC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C=C FYQFWFHDPNXORA-UHFFFAOYSA-N 0.000 description 1
- QRRGZVPIVBHZCM-UHFFFAOYSA-N 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooct-1-yne Chemical compound FC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C#C QRRGZVPIVBHZCM-UHFFFAOYSA-N 0.000 description 1
- NGCDGKUNFPGULT-UHFFFAOYSA-N 3,3,4,4,5,5,6,6,7,7-decafluoronona-1,8-diene Chemical compound C=CC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C=C NGCDGKUNFPGULT-UHFFFAOYSA-N 0.000 description 1
- AKAQZCPDRXZZJS-UHFFFAOYSA-N 3,3,4,4-tetrafluorohexa-1,5-diene Chemical compound C=CC(F)(F)C(F)(F)C=C AKAQZCPDRXZZJS-UHFFFAOYSA-N 0.000 description 1
- BWGRDBSNKQABCB-UHFFFAOYSA-N 4,4-difluoro-N-[3-[3-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl]-1-thiophen-2-ylpropyl]cyclohexane-1-carboxamide Chemical compound CC(C)C1=NN=C(C)N1C1CC2CCC(C1)N2CCC(NC(=O)C1CCC(F)(F)CC1)C1=CC=CS1 BWGRDBSNKQABCB-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 239000004971 Cross linker Substances 0.000 description 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 208000033962 Fontaine progeroid syndrome Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 229910000792 Monel Inorganic materials 0.000 description 1
- LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 238000007259 addition reaction Methods 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 description 1
- 229910001863 barium hydroxide Inorganic materials 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 238000006352 cycloaddition reaction Methods 0.000 description 1
- 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 description 1
- 238000006356 dehydrogenation reaction Methods 0.000 description 1
- 238000005828 desilylation reaction Methods 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 150000002366 halogen compounds Chemical class 0.000 description 1
- 150000002367 halogens Chemical group 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
- 239000000347 magnesium hydroxide Substances 0.000 description 1
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 125000005010 perfluoroalkyl group Chemical group 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 238000011403 purification operation Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000006884 silylation reaction Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
- 150000003613 toluenes Chemical class 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229960003986 tuaminoheptane Drugs 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
Description
特許文献2:欧州特許出願公開第0083274号明細書
非特許文献2:Journal оf Fluorine Chemistry,1994年,第68巻,21頁−24頁。
非特許文献3:Journal оf Fluorine Chemistry,1988年,第38巻,119頁−123頁。
本発明は、下記一般式(1)
で表される含フッ素アルキン化合物に係る。さらに式(1)中のmは2又は4である含フッ素アルキン化合物であることが好ましい。
当該一般式(3)で示される化合物に塩基性化合物を反応させて、下記一般式(4)
上記の通り、本発明の含フッ素アルキン化合物の製造方法は、下記一般式(2)
当該一般式(3)で示される化合物に塩基性化合物を反応させて、下記一般式(4)
1H NMR、19F NMR:ブルカー・バイオスピン株式会社製 AVANCE−III NMR分光計
IR:島津製作所製 IRAffinity フーリエ変換型赤外分光光度計
GC−MS:島津製作所製GCMS−QP2010Plus.
1H NMR(400MHz,CDCl3):
δ=4.50(m,2H),4.03 (dd,J=12.0,3.3Hz,2H),3.61(dd,J=12.0,3.3Hz,2H).
19F NMR(376MHz,CDCl3):δ=−108.83〜−110.12(m,4F),−112.25〜−113.50(m,2F),−117.34〜−120.12(m,2F)。
1H NMR(400MHz,CDCl3):δ=6.49(s,2H),6.21(s,2H).
19F NMR(376MHz,CDCl3):δ=−108.47(s,4F),−119.97(s,4F)。
1H NMR(400MHz,CDCl3):δ=3.05(t,J=5.5Hz,2H).
19F NMR(376MHz,CDCl3):δ=−99.53〜−99.42(m,4F),−122.03〜−121.94(m,4F).
IR(neat):3308cm−1(C−H),2133cm-1(C≡C)。
アルゴン雰囲気下、カリウムtert‐ブトキシド(和光純薬工業製,2.20g,19.6mmol)の脱水テトラヒドロフラン(和光純薬工業製,60mL)溶液を−78℃に冷却した。そこへ、実施例1と同様に得た化合物3(1.00g, 2.43mmol)の脱水テトラヒドロフラン(和光純薬工業製,15mL)溶液をゆっくりと滴下し、−78℃で2時間撹拌した。その後、実施例1と同様の後処理を実施した結果、目的物である化合物4が得られていることが分かった(収率100%)。
アルゴン雰囲気下、ジイソプロピルアミン(和光純薬工業製,1.6mL,11.0mmol)の脱水テトラヒドロフラン(和光純薬工業製,60mL)溶液を−78℃に冷却し、n−ブチルリチウムのn−ヘキサン溶液(関東化学製,7.0mL,11.0mmоl)をゆっくり加え、リチウムジイソプロピルアミドの溶液を調製した。そこへ、実施例1と同様に得た化合物3(1.00g, 2.43mmol)の脱水テトラヒドロフラン(和光純薬工業製,15mL)溶液をゆっくりと滴下し、−78℃で1時間撹拌した。その後、実施例1と同様の後処理を実施した結果、目的物である化合物4が得られていることが分かった(収率100%)。
1H NMR(400MHz,CDCl3):δ=4.47〜4.38(m,2H),3.96(dd,J=12.1,3.4Hz,2H),3.55(dd,J=12.1,3.4Hz,2H).
19F NMR(376MHz,CDCl3):δ=−109.12〜−110.39(m,2F),−112.11〜−113.23(m,2F),−117.43〜−120.19(m,4F),−120.48〜−122.50(m,4F)。
1H NMR(400MHz,CDCl3):δ=6.51(s,2H),6.23(s,2H).
19F NMR(376MHz,CDCl3):δ=−108.47(s,4F),−120.38(s,4F),−121.52(s,4F)。
1H NMR(400MHz,CDCl3):δ=3.01(t,J=5.6Hz,2H).
19F NMR(376MHz,CDCl3):δ=−99.24(s,4F),−121.19(m,4F),−122.71(s,4F).
IR(neat):3310cm−1(C−H),2225cm-1(C≡C)。
1H NMR(400MHz,CDCl3):δ=4.57〜4.48(m,2H),4.05〜4.00(dd,J=12.0,4.4Hz,2H),3.63〜3.57(dd,J=12.0,4.4Hz,2H).
19F NMR(376MHz,CDCl3):δ=−104.91〜−106.77(m,2F),−109.84〜−111.98(m,2F)。
1H NMR(400MHz,CDCl3):δ=6.43(d,2H,J=2.8Hz),6.12(d,2H,J=2.8Hz).
19F NMR(376MHz,CDCl3):δ=−107.78(s,4F)。
GC−MS:231(M−79,40),212(3),181(4),155(100),151(60),129(45),107(13),75(50),57(20),51(15).
1H NMR(400MHz,CDCl3):δ=2.73〜2.76(m,2H).
19F NMR(376MHz,CDCl3):δ=−101.59〜101.58(m,4F).
GC−MS:150(M,3),131(2),124(1),100(10),81(28),75(100),61(7),56(30),50(15),37(9).
窒素雰囲気下、カリウムtert‐ブトキシド(和光純薬工業製,5.20g,46.3mmol)の脱水ジエチルエーテル(和光純薬工業製,70mL)溶液を−70〜−60℃に冷却した。そこへ、実施例5と同様に得たジクロロメタンをわずかに含む化合物10(3.70g, 7.42mmol,純度95wt%)の脱水ジエチルエーテル(和光純薬工業製,6mL)溶液をゆっくりと滴下し、−70〜−60℃で1時間撹拌し、0℃まで昇温した。その後、塩酸水溶液(1M,20mL)を加えて反応を停止した後、飽和食塩水とジエチルエーテルを加えて有機層を抽出し、回収した有機層を無水硫酸マグネシウムで乾燥した。硫酸マグネシウムをろ別した後、ろ液の19FNMR分析から、3,3,4,4−テトラフルオロ−1,5−ヘキサジイン(12)が0.34g(2.27mmоl,収率31%)、化合物11が1.57g(5.03mmоl,収率68%)含まれていることが分かった。
窒素雰囲気下、ナトリウムtert‐ブトキシド(和光純薬工業製,13.48g,140.3mmol)とカリウムtert‐ブトキシド(6.42g,57.2mmol)、溶媒として脱水n−ヘプタン(和光純薬工業製,200mL)と脱水トルエン(和光純薬工業製,50mL)を共存させ、−50〜−40℃に冷却した。そこへ実施例5と同様に得たジクロロメタンをわずかに含む化合物10(7.00g, 14.0mmol,純度95wt%)の脱水n−ヘプタン(和光純薬工業製,8mL)溶液をゆっくりと滴下した。次いで、室温まで昇温し、そのまま室温で16時間攪拌した。塩酸水溶液(1M,300mL)を加えて反応を停止した後、有機層を回収し無水硫酸マグネシウムで乾燥した。硫酸マグネシウムをろ別した後、ろ液の19FNMR分析から、3,3,4,4−テトラフルオロ−1,5−ヘキサジイン(12)が1.05g(7.02mmоl,収率50%)、化合物11が1.44g(4.62mmоl,収率33%)含まれていることが分かった。
1H NMR(400MHz,CDCl3):δ=4.52〜4.43(m,1H),4.03〜3.99(dd,J=12.0,3.6Hz,1H),3.63〜3.58(m,1H).
19F NMR(376MHz,CDCl3):δ=−81.32(t,J=9.8Hz,3F),110.33〜−113.69(m,2F),−119.03〜−121.72(m,2F),−126.26〜−126.37(m,2F).
1H NMR(400MHz,CDCl3):δ=6.51(d,J=3.2Hz,1H),6.25〜6.24(m,1H).
19F NMR(376MHz,CDCl3):δ=−81.38(m,3F),109.10〜−109.17(m,2F),−121.72〜−121.79(m,2F),−126.29〜−126.37(m,2F).
1H NMR(400MHz,CDCl3):δ=2.92(s,1H).
19F NMR(376MHz,CDCl3):δ=−81.59(t,J=9.8Hz,3F),99.51(d,J=2.6Hz,2F),−123.98〜−124.00(m,2F),−125.88〜−125.93(m,2F).
1H NMR(400MHz,CDCl3):δ=4.55〜4.45(m,1H),4.04〜4.00(dd,J=12.0,3.6Hz,1H),3.65〜3.60(m,1H).
19F NMR(376MHz,CDCl3):δ=−81.30(m,3F),110.04〜−113.44(m,2F),−118.11〜−119.87(m,2F),−122.16〜−122.27(m,2F),−123.13〜−123.14(m,2F),−126.56〜−126.60(m,2F).
1H NMR(400MHz,CDCl3):δ=6.52(d,J=3.2Hz,1H),6.25〜6.24(m,1H).
19F NMR(376MHz,CDCl3):δ=−81.37(t,J=9.8Hz,3F),108.91〜−108.99(m,2F),−120.82〜−120.88(m,2F),−122.14〜−122.15(m,2F),−123.28〜−123.29(m,2F),−126.62〜−126.72(m,2F).
1H NMR(400MHz,CDCl3):δ=2.94(s,1H).
19F NMR(376MHz,CDCl3):δ=−81.45(t,J=9.8Hz,3F),98.99(d,J=2.6Hz,2F),−121.77〜−121.79(m,2F),−123.27〜−123.28(m,4F),−126.64〜−126.72(m,2F).
Claims (10)
- 一般式(5)のmが2又は4である請求項1に記載の含フッ素アルキン化合物。
- 一般式(2)中のPがビニル基であり、一般式(3)中のQがハロゲン化エチル基であり、一般式(4)中のRがアセチニル基であり、かつ一般式(5)中のSがハロゲン化ビニル基である請求項3又は請求項4に記載の含フッ素アルキン化合物の製造方法。
- 一般式(2)中のnが2、4又は6である、請求項3〜5のいずれか一項に記載の含フッ素アルキン化合物の製造方法。
- 前記塩基性化合物Aが無機塩基性化合物及び/又はアミン化合物である、請求項3〜6の何れか一項に記載の含フッ素アルキン化合物の製造方法。
- 前記塩基性化合物Bが、アルカリ金属の水素化物、アルカリ金属のアミド化合物及びアルカリ金属のアルコキシド化合物からなる群より選ばれる、請求項3〜7の何れか一項に記載の含フッ素アルキ
- 前記一般式(3)のXが臭素である、請求項3〜8のいずれか一項に記載の含フッ素アルキン化合物の製造方法。
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WO2022230589A1 (ja) * | 2021-04-27 | 2022-11-03 | ダイキン工業株式会社 | フルオロアルキン化合物の製造方法 |
CN116120149A (zh) * | 2023-04-04 | 2023-05-16 | 北京宇极科技发展有限公司 | 饱和卤代烃脱卤化氢制备含氟炔的方法 |
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EP3797999A1 (en) | 2019-09-24 | 2021-03-31 | Seiko Epson Corporation | Recording apparatus |
EP4212344A1 (en) | 2019-09-24 | 2023-07-19 | Seiko Epson Corporation | Recording apparatus |
WO2022230589A1 (ja) * | 2021-04-27 | 2022-11-03 | ダイキン工業株式会社 | フルオロアルキン化合物の製造方法 |
JP2022169343A (ja) * | 2021-04-27 | 2022-11-09 | ダイキン工業株式会社 | フルオロアルキン化合物の製造方法 |
JP7343796B2 (ja) | 2021-04-27 | 2023-09-13 | ダイキン工業株式会社 | フルオロアルキン化合物の製造方法 |
CN116120149A (zh) * | 2023-04-04 | 2023-05-16 | 北京宇极科技发展有限公司 | 饱和卤代烃脱卤化氢制备含氟炔的方法 |
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