KR20150075156A - Novel 2-vinylphenyl phosphate derivatives and its preparation method - Google Patents
Novel 2-vinylphenyl phosphate derivatives and its preparation method Download PDFInfo
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- KR20150075156A KR20150075156A KR1020130162353A KR20130162353A KR20150075156A KR 20150075156 A KR20150075156 A KR 20150075156A KR 1020130162353 A KR1020130162353 A KR 1020130162353A KR 20130162353 A KR20130162353 A KR 20130162353A KR 20150075156 A KR20150075156 A KR 20150075156A
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- alkyl
- mmol
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- KTVWCJUQJUOBOF-UHFFFAOYSA-N (2-ethenylphenyl) dihydrogen phosphate Chemical class OP(O)(=O)OC1=CC=CC=C1C=C KTVWCJUQJUOBOF-UHFFFAOYSA-N 0.000 title claims 2
- 238000002360 preparation method Methods 0.000 title description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims abstract description 58
- -1 2-vinylphenyl phosphate derivative compound Chemical class 0.000 claims abstract description 45
- 238000000034 method Methods 0.000 claims abstract description 16
- 239000003054 catalyst Substances 0.000 claims abstract description 15
- 229910052763 palladium Inorganic materials 0.000 claims abstract description 13
- 239000000654 additive Substances 0.000 claims abstract description 12
- 230000000996 additive effect Effects 0.000 claims abstract description 12
- 229920002554 vinyl polymer Polymers 0.000 claims abstract description 11
- CQLFBEKRDQMJLZ-UHFFFAOYSA-M silver acetate Chemical compound [Ag+].CC([O-])=O CQLFBEKRDQMJLZ-UHFFFAOYSA-M 0.000 claims description 26
- 125000000923 (C1-C30) alkyl group Chemical group 0.000 claims description 18
- 125000003118 aryl group Chemical group 0.000 claims description 16
- 150000001875 compounds Chemical class 0.000 claims description 16
- 125000003545 alkoxy group Chemical group 0.000 claims description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- 239000001257 hydrogen Substances 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 239000000126 substance Substances 0.000 claims description 9
- 101150003085 Pdcl gene Proteins 0.000 claims description 8
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 6
- 229910019142 PO4 Inorganic materials 0.000 claims description 6
- 125000004450 alkenylene group Chemical group 0.000 claims description 6
- 125000004419 alkynylene group Chemical group 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 150000002367 halogens Chemical class 0.000 claims description 6
- 239000010452 phosphate Substances 0.000 claims description 6
- 125000006651 (C3-C20) cycloalkyl group Chemical group 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 125000000027 (C1-C10) alkoxy group Chemical group 0.000 claims description 4
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 claims description 4
- 150000003013 phosphoric acid derivatives Chemical class 0.000 claims description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 3
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 2
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims description 2
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical group C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 2
- 239000005977 Ethylene Substances 0.000 claims description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 2
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Chemical group C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 125000005677 ethinylene group Chemical group [*:2]C#C[*:1] 0.000 claims description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 2
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 2
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 2
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims 5
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 claims 4
- LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 claims 4
- 150000002431 hydrogen Chemical class 0.000 claims 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 2
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 claims 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 claims 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 abstract description 60
- 239000003814 drug Substances 0.000 abstract description 4
- 230000003213 activating effect Effects 0.000 abstract description 3
- 229940079593 drug Drugs 0.000 abstract description 3
- CMPQUABWPXYYSH-UHFFFAOYSA-N phenyl phosphate Chemical group OP(O)(=O)OC1=CC=CC=C1 CMPQUABWPXYYSH-UHFFFAOYSA-N 0.000 abstract description 3
- 239000005445 natural material Substances 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 72
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 69
- 239000002904 solvent Substances 0.000 description 52
- 239000007858 starting material Substances 0.000 description 48
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 46
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 46
- ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 25
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 24
- 235000019439 ethyl acetate Nutrition 0.000 description 23
- 239000010410 layer Substances 0.000 description 23
- 239000012044 organic layer Substances 0.000 description 23
- 238000005481 NMR spectroscopy Methods 0.000 description 22
- 238000004440 column chromatography Methods 0.000 description 22
- 230000015572 biosynthetic process Effects 0.000 description 18
- 238000003786 synthesis reaction Methods 0.000 description 18
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 15
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 15
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 12
- XTBBZRRBOAVBRA-UHFFFAOYSA-N dimethyl phenyl phosphate Chemical compound COP(=O)(OC)OC1=CC=CC=C1 XTBBZRRBOAVBRA-UHFFFAOYSA-N 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- FPRUZLWZQCUGMX-UHFFFAOYSA-N (2,3-dimethylphenyl) methyl hydrogen phosphate Chemical compound COP(O)(=O)OC1=CC=CC(C)=C1C FPRUZLWZQCUGMX-UHFFFAOYSA-N 0.000 description 5
- ZMXDDKWLCZADIW-UHFFFAOYSA-N Vilsmeier-Haack reagent Natural products CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 125000001072 heteroaryl group Chemical group 0.000 description 3
- 239000002547 new drug Substances 0.000 description 3
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-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
- 230000004913 activation Effects 0.000 description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 229940113088 dimethylacetamide Drugs 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 230000009257 reactivity Effects 0.000 description 2
- 238000001308 synthesis method Methods 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
- DCQMRNZNRJSQAP-UHFFFAOYSA-N (2,3-dimethylphenyl) dimethyl phosphate Chemical compound P(=O)(OC1=C(C(=CC=C1)C)C)(OC)OC DCQMRNZNRJSQAP-UHFFFAOYSA-N 0.000 description 1
- WWRQYCXFGVBMSA-UHFFFAOYSA-N (2-fluorophenyl) methyl hydrogen phosphate Chemical compound P(=O)(OC1=C(C=CC=C1)F)(OC)O WWRQYCXFGVBMSA-UHFFFAOYSA-N 0.000 description 1
- SVMDLHOOWKXZJT-UHFFFAOYSA-N (2-tert-butylphenyl) methyl hydrogen phosphate Chemical compound P(=O)(OC1=C(C=CC=C1)C(C)(C)C)(OC)O SVMDLHOOWKXZJT-UHFFFAOYSA-N 0.000 description 1
- QVKJHFCFHUAYAK-UHFFFAOYSA-N (3,4-dimethoxyphenyl) methyl hydrogen phosphate Chemical compound P(=O)(OC1=CC(=C(C=C1)OC)OC)(OC)O QVKJHFCFHUAYAK-UHFFFAOYSA-N 0.000 description 1
- SPWROUSGUDAHQP-UHFFFAOYSA-N (3-methoxyphenyl) methyl hydrogen phosphate Chemical compound O(C)C=1C=C(C=CC1)OP(OC)(O)=O SPWROUSGUDAHQP-UHFFFAOYSA-N 0.000 description 1
- VQQFRVPFJWHMEL-UHFFFAOYSA-N (3-tert-butylphenyl) methyl hydrogen phosphate Chemical compound P(=O)(OC1=CC(=CC=C1)C(C)(C)C)(OC)O VQQFRVPFJWHMEL-UHFFFAOYSA-N 0.000 description 1
- BMCCMYMIMLSPPJ-UHFFFAOYSA-N (4-chloro-2-methylphenyl) methyl hydrogen phosphate Chemical compound P(=O)(OC1=C(C=C(C=C1)Cl)C)(OC)O BMCCMYMIMLSPPJ-UHFFFAOYSA-N 0.000 description 1
- DREPONDJUKIQLX-UHFFFAOYSA-N 1-[ethenyl(ethoxy)phosphoryl]oxyethane Chemical compound CCOP(=O)(C=C)OCC DREPONDJUKIQLX-UHFFFAOYSA-N 0.000 description 1
- KTZVZZJJVJQZHV-UHFFFAOYSA-N 1-chloro-4-ethenylbenzene Chemical compound ClC1=CC=C(C=C)C=C1 KTZVZZJJVJQZHV-UHFFFAOYSA-N 0.000 description 1
- LVJZCPNIJXVIAT-UHFFFAOYSA-N 1-ethenyl-2,3,4,5,6-pentafluorobenzene Chemical compound FC1=C(F)C(F)=C(C=C)C(F)=C1F LVJZCPNIJXVIAT-UHFFFAOYSA-N 0.000 description 1
- IGGDKDTUCAWDAN-UHFFFAOYSA-N 1-vinylnaphthalene Chemical compound C1=CC=C2C(C=C)=CC=CC2=C1 IGGDKDTUCAWDAN-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
- JHUUPUMBZGWODW-UHFFFAOYSA-N 3,6-dihydro-1,2-dioxine Chemical compound C1OOCC=C1 JHUUPUMBZGWODW-UHFFFAOYSA-N 0.000 description 1
- ATAVTRQWCYQMHZ-VAWYXSNFSA-N CCOP(=O)(/C=C/C1=C(C(=C(C=C1)C)C)OP(=O)(OC)OC)OCC Chemical compound CCOP(=O)(/C=C/C1=C(C(=C(C=C1)C)C)OP(=O)(OC)OC)OCC ATAVTRQWCYQMHZ-VAWYXSNFSA-N 0.000 description 1
- 238000010499 C–H functionalization reaction Methods 0.000 description 1
- AFGILAVFUHYCFL-UXBLZVDNSA-N P(=O)(OC1=C(C(=CC=C1\C=C\C1=CC=C(C=C1)Cl)C)C)(OC)OC Chemical compound P(=O)(OC1=C(C(=CC=C1\C=C\C1=CC=C(C=C1)Cl)C)C)(OC)OC AFGILAVFUHYCFL-UXBLZVDNSA-N 0.000 description 1
- WRSCQUWYGNISQI-UHFFFAOYSA-N P(=O)(OC1=C(C=C(C=C1)C)C1C2CC3CC(CC1C3)C2)(OC)O Chemical compound P(=O)(OC1=C(C=C(C=C1)C)C1C2CC3CC(CC1C3)C2)(OC)O WRSCQUWYGNISQI-UHFFFAOYSA-N 0.000 description 1
- DGWFTXFBEWETJB-UHFFFAOYSA-N P(=O)(OC1=C(C=CC=C1)CC1=CC=CC=C1)(OC)O Chemical compound P(=O)(OC1=C(C=CC=C1)CC1=CC=CC=C1)(OC)O DGWFTXFBEWETJB-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
- 125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 1
- 150000001555 benzenes Chemical class 0.000 description 1
- GCTPMLUUWLLESL-UHFFFAOYSA-N benzyl prop-2-enoate Chemical compound C=CC(=O)OCC1=CC=CC=C1 GCTPMLUUWLLESL-UHFFFAOYSA-N 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 238000006664 bond formation reaction Methods 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- UJTPZISIAWDGFF-UHFFFAOYSA-N ethenylsulfonylbenzene Chemical compound C=CS(=O)(=O)C1=CC=CC=C1 UJTPZISIAWDGFF-UHFFFAOYSA-N 0.000 description 1
- ILTQGDMVKLZGPZ-MDZDMXLPSA-N ethyl (E)-3-(2-dimethoxyphosphoryloxy-3-methylphenyl)prop-2-enoate Chemical compound COP(=O)(OC)OC1=C(C=CC=C1C)/C=C/C(=O)OCC ILTQGDMVKLZGPZ-MDZDMXLPSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- RWFXKDOCHAHZOT-UHFFFAOYSA-N methyl (2-methylphenyl) hydrogen phosphate Chemical compound COP(O)(=O)OC1=CC=CC=C1C RWFXKDOCHAHZOT-UHFFFAOYSA-N 0.000 description 1
- CAAULPUQFIIOTL-UHFFFAOYSA-M methyl hydrogen phosphate Chemical compound COP(O)([O-])=O CAAULPUQFIIOTL-UHFFFAOYSA-M 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 150000002903 organophosphorus compounds Chemical class 0.000 description 1
- 210000003899 penis Anatomy 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 238000006557 surface reaction Methods 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
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/08—Esters of oxyacids of phosphorus
- C07F9/09—Esters of phosphoric acids
- C07F9/12—Esters of phosphoric acids with hydroxyaryl compounds
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J23/00—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00
- B01J23/38—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of noble metals
- B01J23/40—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of noble metals of the platinum group metals
- B01J23/44—Palladium
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
- C09B23/00—Methine or polymethine dyes, e.g. cyanine dyes
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
Abstract
Description
본 발명은 2-바이닐페닐 포스페이트 유도체 화합물과 이의 제조방법에 관한 것으로, 보다 상세하게, 신규한 2-바이닐페닐 포스페이트 유도체와 자리선택성에 적합한 지향성기를 사용한 효율적인 제조방법에 관한 것이다. The present invention relates to a 2-vinylphenylphosphate derivative compound and a process for producing the same, and more particularly, to an efficient process for producing a novel 2-vinylphenylphosphate derivative and a directivity group suitable for site selectivity.
유기인 화합물은 생물의 중요한 성분이며 생물학적 활성과 새로운 의약품을 합성, 유기촉매로 이용 할 수 있는 가능성을 지니고 있기 때문에 그 합성에 많은 관심을 갖고 있다.Organophosphorus compounds are an important component of organisms and have a great interest in synthesis because they have the potential to use biological activity and new drugs as synthetic and organic catalysts.
촉매와 지향성 기를 이용한 탄소-수소 결합 활성화 반응은 지난 몇 년간의 수많은 연구를 통하여 기존의 짝지움 반응이 갖고 있는 환경적/경제적인 문제를 많은 부분 해결하였다. 이에 따라 다양한 지향성 기의 개발은 탄소-수소 결합 활성화 반응의 진행여부에 핵심적인 요인이 된다. 특히 벤젠 유도체에서, C-H 결합 사이의 반응성이 다르기 때문에 자리 선택성을 제어 할 수 있는 방법이 필요하다. 최근 몇 년 동안 새로운 지향성 기의 도입을 통해 자리 선택성을 극복한 C-C 및 C-헤테로 원자 결합 형성 반응의 예들이 보고 되었다. 지향성기의 사용이 선택적으로 작용기를 도입하는 실질적인 합성법이 되었지만, 이 방법은 대부분의 경우에, 지향성기가 도입된 arene에 ortho C-H 결합의 반응성을 증가시켰다. 또한, 많은 지향성 기는 피리딘, 카르복실 산 또는 그 유도체 내에 제한되어 있다. 따라서 새로운 실용적인 지향성기의 개발이 중요하다 (Acc . Chem . Res . 2012 , 45, 788; Chem . Rev. 2011, 111, 1215; Chem . Soc . Rev . 2011, 40, 4740; Chem . Commun. 2010, 46, 677; Chem . Rev. 2010, 110, 1147; Chem . Soc . Rev . 2011, 40, 5068 Acc . Chem . Res. 1979, 12, 146; Org . React. 1982, 27, 345; Chem . Rev. 2000, 100, 3009; Chem . Rev. 2003, 103, 2945; Synthesis 2010, 12, 1929; Chem . Commun . 2008, 4097; Angew . Chem . Int . Ed . 2012, 51, 9684).Carbon - hydrogen bond activation using catalysts and directivities has largely solved the environmental and economic problems of existing coupling reactions through numerous studies over the last few years. Therefore, the development of various directivities is a key factor in the progress of the carbon - hydrogen bonding activation reaction. Especially in benzene derivatives, there is a need for a method that can control the site selectivity because the reactivity between CH bonds is different. In recent years, examples of CC and C-heteroatom bond formation reactions have been reported overcoming digit selectivity through the introduction of a new directivity group. Although the use of directing groups has become a practical synthesis method to selectively introduce functional groups, in most cases this method has increased the reactivity of ortho CH bonds to the arene in which the directing group is introduced. In addition, many of the directing groups are limited within pyridine, carboxylic acid or derivatives thereof. Therefore, the development of a new practical orientation penis is important ( Acc . Chem . Res . 2012 , 45, 788; Chem . Rev. 2011 , 111 , 1215; Chem . Soc . Rev. 2011 , 40 , 4740; Chem . Commun . 2010 , 46, 677; Chem . Rev. 2010 , 110 , 1147; Chem . Soc . Rev. 2011 , 40 , 5068 Acc . Chem . Res . 1979 , 12 , 146; Org . React . 1982 , 27 , 345; Chem . Rev. 2000 , 100 , 3009; Chem . Rev. 2003 , 103 , 2945; Synthesis 2010 , 12 , 1929; Chem . Commun . 2008 , 4097; Angew . Chem . Int . Ed . 2012 , 51 , 9684).
현재 dimethyl phenyl phosphate 또는 그 유도체를 지향성 기로 갖는 C-H 결합 활성화 반응과 이 반응을 통해 다이메틸 2-바이닐페닐 포스페이트 유도체를 제조하는 방법은 보고되지 않았다. 따라서, 생물학적 활성을 가지고 있는 포스페이트 유도체에 관해 효율적인 합성법이 여전히 요구되고 있는 실정이다.At present, there has not been reported a C-H bond activation reaction having a dimethyl phenyl phosphate or a derivative thereof as a directing group and a process for producing a dimethyl 2-vinylphenylphosphate derivative through this reaction. Therefore, there is still a need for efficient synthesis methods for phosphate derivatives having biological activity.
본 발명의 목적은 신규한 2-바이닐페닐 포스페이트 유도체 화합물을 제공한다.An object of the present invention is to provide a novel 2-vinylphenylphosphate derivative compound.
또한, 본 발명은 자리선택성에 적합한 지향성기를 사용한 효율적인 신규한 2-바이닐페닐 포스페이트 유도체화합물의 제조방법을 제공하고자 한다. In addition, the present invention aims to provide a novel method for producing a novel 2-vinylphenylphosphine derivative compound using a directing group suitable for digit selectivity.
본 발명은 하기 화학식 1로 표시되는 2-바이닐페닐 포스페이트 유도체 화합물을 제공하고자 한다.The present invention provides a 2-vinylphenylphosphate derivative represented by the following general formula (1).
[화학식 1][Chemical Formula 1]
상기 화학식 1에서 R1은 (C1-C30)알킬, (C6-C30)아릴, (C6-C30)아르(C1-C20)알킬, -C(=O)Ra,-C(=O)ORa, -S(=O)2Ra 및 -P(=O)(Ra)2 로부터 선택되어지고, 상기 Ra는 (C1-C30)알킬, (C1-C20)알콕시, (C6-C30)아릴 및 (C6-C30)아르(C1-C20)알킬로부터 선택되어지고, 상기 아릴은 할로겐 또는 (C1-C10)알킬로 더 치환될 수 있으며, R2 내지 R5 는 서로 독립적으로 할로겐, (C1-C30)알킬, (C1-C20)알콕시 및 (C3-C20)사이클로알킬로부터 선택되어지고, R4 와 R5는 인접한 (C2-C10)알케닐렌 또는 (C2-C10)알키닐렌으로 연결되어 고리를 형성 할 수 있으며, R6 및 R7은 서로 독립적으로 수소, 하이드록시, (C1-C10)알킬 및 (C1-C10)알콕시로부터 선택될 수 있다.In the general formula 1 R 1 is (C1-C30) alkyl, (C6-C30) aryl, (C6-C30) aralkyl (C1-C20) alkyl, -C (= O) R a , -C (= O) OR a, from -S (= O) 2 R a, and -P (= O) (R a ) 2 Selected, Wherein R a is selected from (C 1 -C 30) alkyl, (C 1 -C 20) alkoxy, (C 6 -C 30) aryl and (C 6 -C 30) C10) alkyl, < / RTI > R 2 To R 5 are independently selected from halogen, (C 1 -C 30) alkyl, (C 1 -C 20) alkoxy and (C 3 -C 20) cycloalkyl, R 4 and R 5 are selected from the group consisting of adjacent (C 2 -C 10) alkenylene or (C 1 -C 10) alkynylene, and R 6 and R 7 may be independently selected from hydrogen, hydroxy, (C 1 -C 10) alkyl and (C 1 -C 10) alkoxy.
보다 더 구체적으로, 상기 화학식 1에서 R1은 에톡시카보닐, 벤질옥시카보닐, 1-나프틸, 페닐, 파라클로로페닐, 헥사클로로페닐, 벤조일, 다이에틸포스포릴 및 페닐썰포닐로부터 선택되며, R3 내지 R5 는 서로 독립적으로 수소, 메틸, t-부틸, 메톡시, 페닐, 벤질, 아다만틸, 플로로 및 클로로로부터 선택되며,More specifically, in Formula 1, R 1 is selected from ethoxycarbonyl, benzyloxycarbonyl, 1-naphthyl, phenyl, para chlorophenyl, hexachlorophenyl, benzoyl, diethylphosphoryl and phenylsulfonyl , R 3 to R 5 independently from each other are selected from hydrogen, methyl, t-butyl, methoxy, phenyl, benzyl, adamantyl, fluoro and chloro,
상기 R4 와 R5는 인접한 에틸렌 또는 아세틸렌으로 연결되어 
본 발명의 신규한 2-바이닐페닐 포스페이트 유도체 화합물인 상기 화학식 1은 하기 구조식으로 선택될 수 있으나, 이에 한정이 있는 것은 아니다. The novel 2-vinylphenylphosphate derivative compound of the present invention, represented by Formula 1, may be selected from the following structural formulas, but is not limited thereto.
본 발명은 팔라듐 촉매 및 첨가제 존재 하 하기 화학식 2로 표시되는 포스페이트 화합물과 하기 화학식 3으로 표시되는 바이닐 화합물을 반응시켜 하기 화학식 1의 2-바이닐페닐 포스페이트 유도체 화합물의 제조 방법을 제공한다.
The present invention provides a process for preparing a 2-vinylphenylphosphate derivative represented by the following formula (1) by reacting a phosphate compound represented by the following formula (2) with a vinyl compound represented by the following formula (3) in the presence of a palladium catalyst and an additive.
[화학식 2] (2)
[화학식 3](3)
[화학식 1][Chemical Formula 1]
상기 화학식 1 및 화학식 3에서 R1은 (C1-C30)알킬, (C6-C30)아릴, (C6-C30)아르(C1-C20)알킬, -C(=O)Ra,-C(=O)ORa, -S(=O)2Ra 및 -P(=O)(Ra)2 로부터 선택되어지고, 상기 Ra는 (C1-C30)알킬, (C1-C20)알콕시, (C6-C30)아릴 및 (C6-C30)아르(C1-C20)알킬로부터 선택되어지고, 상기 아릴은 할로겐 또는 (C1-C10)알킬로 더 치환될 수 있으며, 상기 화학식 1 및 화학식 2에서 R2 내지 R5 는 서로 독립적으로 할로겐, (C1-C30)알킬, (C1-C20)알콕시 및 (C3-C20)사이클로알킬로부터 선택되어지고, R4 와 R5는 인접한 (C2-C10)알케닐렌 또는 (C2-C10)알키닐렌으로 연결되어 고리를 형성 할 수 있으며, 상기 화학식 1 및 화학식 2에서 R6 및 R7은 서로 독립적으로 수소, 하이드록시, (C1-C10)알킬 및 (C1-C10)알콕시로부터 선택될 수 있다.In Formula 1 and Formula 3 R 1 is (C1-C30) alkyl, (C6-C30) aryl, (C6-C30) aralkyl (C1-C20) alkyl, -C (= O) R a , -C (= O) OR a , -S (= O) 2 R a and -P (= O) (R a ) 2 Selected, Wherein R a is selected from (C 1 -C 30) alkyl, (C 1 -C 20) alkoxy, (C 6 -C 30) aryl and (C 6 -C 30) C10) alkyl, < / RTI > In the above formulas (1) and (2), R 2 To R 5 are independently selected from halogen, (C 1 -C 30) alkyl, (C 1 -C 20) alkoxy and (C 3 -C 20) cycloalkyl, R 4 and R 5 are selected from the group consisting of adjacent (C 2 -C 10) alkenylene or (C2-C10) connected to the alkynylene can form a ring, the formula (1) and R 6 and R 7 are independently hydrogen, hydroxy, (C1-C10) alkyl and (C1-C10) to each other in the general formula (2) Alkoxy. ≪ / RTI >
본 발명의 일 실시예에 따른 팔라듐(Pd) 촉매는 Pd(OAc)2 , Pd(TFA)2 , PdCl2, PdBr2, PdCl2(MeCN)2, [(C6H5)3P]2PdCl2 , Pd(dppf)Cl2 및 [PdCl(C3H5)]2 에서 선택되는 하나 이상인 것을 특징으로 하는 2-바이닐페닐 포스페이트 유도체 화합물의 제조방법일 수 있다.Palladium (Pd) catalyst in accordance with one embodiment of the invention is Pd (OAc) 2, Pd ( TFA) 2, PdCl 2, PdBr 2, PdCl 2 (MeCN) 2, [(C 6 H 5) 3 P] 2 PdCl 2 , Pd (dppf) Cl 2, and [PdCl (C 3 H 5 )] 2 .
상기 팔라듐 촉매의 양은 상기 화학식 2로 표시되는 포스페이트 유도체에 대해 0.01 내지 0.5몰을 사용하는 것을 특징으로 하는 2-바이닐페닐 포스페이트 유도체 화합물의 제조방법일 수 있다.The amount of the palladium catalyst may be 0.01 to 0.5 mol based on the amount of the phosphate derivative represented by the formula (2).
본 발명의 일 실시예에 따른 첨가제는 CuCl, Cu2O, CuO, Cu(OAc)2, Cu(OTf)2, Ag2O, AgO, AgOAc, Ag2CO3, Na2K2O8, K2S2O8, NaOAc, BQ, NIS, NCS, FeCl3, Mn(OAc)3 2H2O, V2O5, PhI(OAc)2, PhI(TFA)2, IOAc, Oxone 및 O2에서 선택되는 하나 이상인 것을 특징으로 하는 2-바이닐페닐 포스페이트 유도체 화합물의 제조방법일 수 있다.Additive according to one embodiment of the present invention, CuCl, Cu 2 O, CuO, Cu (OAc) 2, Cu (OTf) 2, Ag 2 O, AgO, AgOAc, Ag 2 CO 3, Na 2 K 2 O 8, K 2 S 2 O 8, NaOAc , BQ, NIS, NCS, FeCl 3, Mn (OAc) 3 2H 2 O, V 2 O 5, PhI (OAc) 2, PhI (TFA) 2, IOAc, Oxone , and O 2 And a method for preparing the 2-vinylphenylphosphate derivative compound.
상기 첨가제의 양은 상기 화학식 2로 표시되는 포스페이트 유도체에 대해 1 내지 5몰을 사용하는 다이메틸 2-바이닐페닐 포스페이트 화합물의 제조방법일 수 있다.The amount of the additive may be a method for producing a dimethyl 2-vinylphenylphosphate compound using 1 to 5 moles of the phosphate derivative represented by the formula (2).
본 발명의 일 실시예에 따라 상기 화학식3의 바이닐 화합물은 상기 화학식 2의 화합물에 대해 1 내지 5 몰로 사용하는것을 특징으로 하는 상기 화학식 1의2-바이닐페닐 포스페이트 유도체 화합물의 제조방법일 수 있다.According to an embodiment of the present invention, the vinyl compound of Chemical Formula 3 may be used in an amount of 1 to 5 moles relative to the compound of Chemical Formula 2 in the process of preparing the 2-vinylphenylphosphate derivative of Chemical Formula 1.
본 발명은 팔라듐 촉매와 첨가제를 사용하여 페닐 포스페이트의 원하는 위치의 C-H 결합을 활성화 하여 바이닐 화합물과의 반응을 통해 다양한 구조의 2-바이닐 페닐 포스페이트 유도체 화합물 및 효율적인 제조방법을 제공하였다. The present invention provides a 2-vinylphenylphosphine derivative compound having various structures through a reaction with a vinyl compound by activating a C-H bond at a desired position of phenylphosphate using a palladium catalyst and an additive, and an efficient production method.
또한 본 발명에 의해 제조 된 신규한 2-바이닐페닐 포스페이트 유도체 화합물은 천연물의 기본골격으로 사용될 뿐만 아니라 이를 통해 신약 개발 및 다양한 의약품의 개발이 가능하다. Also, the novel 2-vinylphenylphosphate derivative compound prepared by the present invention can be used not only as a basic skeleton of natural products, but also through the development of new drugs and the development of various medicines.
본 발명에 기재된 「알킬」, 「알콕시」 및 그 외 「알킬」부분을 포함하는 치환체는 직쇄 또는 분쇄 형태를 모두 포함한다. 「사이클로알킬」은 3 내지 20의 탄소수를 갖는 고리를 형성하는 알킬을 포함하며, 예로 아다만틸등을 포함하지만 이에 한정되지 않는다. 또한 본 발명에 기재된 「아릴」은 하나의 수소 제거에 의해서 방향족 탄화수소로부터 유도된 유기 라디칼로, 각고리에 적절하게는 4 내지 7개, 바람직하게는 5 또는 6개의 고리원자를 포함하는 단일 또는 융합고리계를 포함하며, 다수개의 아릴이 단일결합으로 연결되어 있는 형태까지 포함한다. 구체적인 예로 페닐, 나프틸, 비페닐, 안트릴, 인데닐(indenyl), 플루오레닐 등을 포함하지만, 이에 한정되지 않는다. 본 발명에 기재된 「헤테로아릴」은 방향족 고리 골격 원자로서 B, N, O, S, P(=O), Si 및 P로부터 선택되는 1 내지 4개의 헤테로원자를 포함하고, 나머지 방향족 고리 골격 원자가 탄소인 아릴 그룹을 의미하는 것으로, 5 내지 6원 단환 헤테로아릴 및 하나 이상의 벤젠환과 축합된 다환식 헤테로아릴이며, 부분적으로 포화될 수도 있다. 또한, 본 발명에서의 헤테로아릴은 하나 이상의 헤테로아릴이 단일결합으로 연결된 형태도 포함한다.The substituents comprising " alkyl ", " alkoxy " and other " alkyl " moieties described in this invention encompass both linear and branched forms. &Quot; Cycloalkyl " includes alkyl that forms a ring having from 3 to 20 carbon atoms, including, but not limited to, adamantyl and the like. The term " aryl " in the present invention means an organic radical derived from an aromatic hydrocarbon by the removal of one hydrogen, and may be a single or fused ring containing 4 to 7, preferably 5 or 6 ring atoms, A ring system, and a form in which a plurality of aryls are connected by a single bond. Specific examples include, but are not limited to, phenyl, naphthyl, biphenyl, anthryl, indenyl, fluorenyl, and the like. The "heteroaryl" described in the present invention includes 1 to 4 heteroatoms selected from B, N, O, S, P (= O), Si and P as aromatic ring skeletal atoms and the remaining aromatic ring skeletal atoms include carbon Means a 5 to 6 membered monocyclic heteroaryl and a polycyclic heteroaryl condensed with at least one benzene ring and may be partially saturated. The heteroaryl in the present invention also includes a form in which one or more heteroaryl is connected to a single bond.
본 발명은 하기 화학식 1로 표시되는 2-바이닐페닐 포스페이트 유도체 화합물을 제공하고자 한다.The present invention provides a 2-vinylphenylphosphate derivative represented by the following general formula (1).
[화학식 1][Chemical Formula 1]
상기 화학식 1에서 R1은 (C1-C30)알킬, (C6-C30)아릴, (C6-C30)아르(C1-C20)알킬, -C(=O)Ra,-C(=O)ORa, -S(=O)2Ra 및 -P(=O)(Ra)2 로부터 선택되어지고, 상기 Ra는 (C1-C30)알킬, (C1-C20)알콕시, (C6-C30)아릴 및 (C6-C30)아르(C1-C20)알킬로부터 선택되어지고, 상기 아릴은 할로겐 또는 (C1-C10)알킬로 더 치환될 수 있으며, R2 내지 R5 는 서로 독립적으로 할로겐, (C1-C30)알킬, (C1-C20)알콕시 및 (C3-C20)사이클로알킬로부터 선택되어지고, R4 와 R5는 인접한 (C2-C10)알케닐렌 또는 (C2-C10)알키닐렌으로 연결되어 고리를 형성 할 수 있으며, R6 및 R7은 서로 독립적으로 수소, 하이드록시, (C1-C10)알킬 및 (C1-C10)알콕시로부터 선택될 수 있다.In the general formula 1 R 1 is (C1-C30) alkyl, (C6-C30) aryl, (C6-C30) aralkyl (C1-C20) alkyl, -C (= O) R a , -C (= O) OR a, from -S (= O) 2 R a, and -P (= O) (R a ) 2 Selected, Wherein R a is selected from (C 1 -C 30) alkyl, (C 1 -C 20) alkoxy, (C 6 -C 30) aryl and (C 6 -C 30) C10) alkyl, < / RTI > R 2 To R 5 are independently selected from halogen, (C 1 -C 30) alkyl, (C 1 -C 20) alkoxy and (C 3 -C 20) cycloalkyl, R 4 and R 5 are selected from the group consisting of adjacent (C 2 -C 10) alkenylene or (C 1 -C 10) alkynylene, and R 6 and R 7 may be independently selected from hydrogen, hydroxy, (C 1 -C 10) alkyl and (C 1 -C 10) alkoxy.
본 발명의 목적은 팔라듐 촉매를 사용하여 페닐 포스페이트의 ortho-위치에 존재하는 C-H 결합을 활성화 하여 바이닐 화합물과의 반응을 통해 다양한 구조의 생리학적 활성을 가진 신규한 2-바이닐 페닐 포스페이트 유도체 화합물을 제공하여, 천연물의 기본골격으로 사용될 뿐만 아니라 이를 통해 신약 개발 및 다양한 의약품의 개발이 가능할 수 있다.An object of the present invention is to provide a novel 2-vinylphenylphosphate derivative compound having various physiological activities through the reaction with a vinyl compound by activating a CH bond present at the ortho-position of phenylphosphate using a palladium catalyst Thus, it can be used as a basic skeleton of natural products and it is possible to develop new drugs and develop various medicines.
본 발명의 사용되는 기술 용어 및 과학 용어에 있어서 다른 정의가 없다면, 이 발명이 속하는 기술 분야에서 통상의 지식을 가진 자가 통상적으로 이해하고 있는 의미를 가진다. 또한, 종래와 동일한 기술적 구성 및 작용에 대한 반복되는 설명은 생략하기로 한다. Unless defined otherwise in the technical and scientific terms used herein, the meaning is commonly understood by those of ordinary skill in the art to which this invention belongs. Repeated descriptions of the same technical constitution and operation as those of the conventional art will be omitted.
본 발명은 팔라듐촉매 및 첨가제 존재 하 하기 화학식 2로 표시되는 포스페이트 화합물과 하기 화학식 3으로 표시되는 바이닐 화합물을 반응시켜 하기 화학식 1의 2-바이닐페닐 포스페이트 유도체 화합물의 제조 방법을 제공한다.The present invention provides a process for preparing a 2-vinylphenylphosphate derivative represented by the following formula (1) by reacting a phosphate compound represented by the following formula (2) with a vinyl compound represented by the following formula (3) in the presence of a palladium catalyst and an additive.
[화학식 2] (2)
[화학식 3](3)
[화학식 1][Chemical Formula 1]
상기 화학식 1 및 화학식 3에서 R1은 (C1-C30)알킬, (C6-C30)아릴, (C6-C30)아르(C1-C20)알킬, -C(=O)Ra,-C(=O)ORa, -S(=O)2Ra 및 -P(=O)(Ra)2 로부터 선택되어지고, 상기 Ra는 (C1-C30)알킬, (C1-C20)알콕시, (C6-C30)아릴 및 (C6-C30)아르(C1-C20)알킬로부터 선택되어지고, 상기 아릴은 할로겐 또는 (C1-C10)알킬로 더 치환될 수 있으며, 상기 화학식 1 및 화학식 2에서 R2 내지 R5 는 서로 독립적으로 할로겐, (C1-C30)알킬, (C1-C20)알콕시 및 (C3-C20)사이클로알킬로부터 선택되어지고, R4 와 R5는 인접한 (C2-C10)알케닐렌 또는 (C2-C10)알키닐렌으로 연결되어 고리를 형성 할 수 있으며, 상기 화학식 1 및 화학식 2에서 R6 및 R7은 서로 독립적으로 수소, 하이드록시, (C1-C10)알킬 및 (C1-C10)알콕시로부터 선택될 수 있다.In Formula 1 and Formula 3 R 1 is (C1-C30) alkyl, (C6-C30) aryl, (C6-C30) aralkyl (C1-C20) alkyl, -C (= O) R a , -C (= O) OR a , -S (= O) 2 R a and -P (= O) (R a ) 2 Selected, Wherein R a is selected from (C 1 -C 30) alkyl, (C 1 -C 20) alkoxy, (C 6 -C 30) aryl and (C 6 -C 30) C10) alkyl, < / RTI > In the above formulas (1) and (2), R 2 To R 5 are independently selected from halogen, (C 1 -C 30) alkyl, (C 1 -C 20) alkoxy and (C 3 -C 20) cycloalkyl, R 4 and R 5 are selected from the group consisting of adjacent (C 2 -C 10) alkenylene or (C2-C10) connected to the alkynylene can form a ring, the formula (1) and R 6 and R 7 are independently hydrogen, hydroxy, (C1-C10) alkyl and (C1-C10) to each other in the general formula (2) Alkoxy. ≪ / RTI >
보다 더 구체적으로, 효율적인 화학식 1의 화합물을 제조하기 위하여 시작물질인 화학식2의 R6은 하이드록시, R7은 메톡시로 시작하여, 반응 종료 후 TMS-diazomethane을 사용하여 R6의 하이드록시를 메톡시로 변환 하여 효과적인 알켄닐레이션 반응임을 확인 할 수 있었다.More specifically, in order to produce an effective compound of formula (I), R 6 of formula (2), which is a starting material, is hydroxy, R 7 is methoxy, and TMS-diazomethane is used to react with R 6 Methoxy, indicating an effective alkenylation reaction.
반응 효율적인 측면에서 구체적으로 팔라듐 촉매는 Pd(OAc)2일 수 있으며, 첨가제는 AgOAc일 수 있다.In terms of reaction efficiency, specifically, the palladium catalyst may be Pd (OAc) 2 , and the additive may be AgOAc.
본 발명은 상기와 같은 팔라듐 촉매 및 첨가제의 반응조건에서 반응성이 낮고 미리 작용기화 되어 있지 않은 C-H 결합을 활성화하여 바이닐 화합물과의 짝지움 반응을 진행하기 때문에 비용과 반응 단계 및 시간에 있어서 경제적이기에 효율적인 제조방법이다.Since the coupling reaction with a vinyl compound proceeds under the reaction conditions of the palladium catalyst and the additive as described above and the CH bond which is not reacted beforehand is activated, the present invention is economical in cost, reaction step and time, Lt; / RTI >
보다 더 구체적으로, 팔라듐 촉매의 양은 0.05 내지 0.3 몰로 수행될 수 있으며, 첨가제의 양은 2 내지 4몰로 수행될 수 있다.More specifically, the amount of the palladium catalyst may be performed at 0.05 to 0.3 mole, and the amount of the additive may be 2 to 4 mole.
상기 화학식 3은 화학식 2를 기준으로 1 내지 3몰로 수행하는 것이 바람직하다.The formula (3) is preferably performed with 1 to 3 moles based on the formula (2).
본 발명의 제조방법에서 사용되는 용매는 통상의 유기용매이며 1,4-다이옥산 (1,4-dioxane), 다이클로로메탄 (DCM), 다이클로로에탄 (DCE), 톨루엔 (Toluene), 아세토나이트릴 (MeCN), 나이트로메탄 (nitromethan), 테트라하이드로퓨란 (THF), N,N-다이메틸포름아마이드 (DMF) 및 N,N-다이메틸아세트아마이드 (DMA)을 사용하는 것이 바람직하며, 1,4-다이옥산을 용매로 사용하는 것이 더욱 바람직하다. 반응온도는 상온 내지 110 ℃에서 상기 반응을 수행하며, 110 ℃에서 수행하는 것이 더욱 바람직하다.The solvent used in the preparation method of the present invention is a conventional organic solvent and may be selected from the group consisting of 1,4-dioxane, dichloromethane (DCM), dichloroethane (DCE), toluene (Toluene) (MeCN), nitro methane (nitromethan), tetrahydrofuran (THF), N, N - it is preferable to use dimethyl acetamide (DMA), 1, - dimethylformamide (DMF) and N, N It is more preferable to use 4-dioxane as a solvent. The reaction is carried out at a temperature ranging from room temperature to 110 ° C, and more preferably at 110 ° C.
반응시간은 반응물질, 용매의 종류 및 용매의 양에 따라 달라질 수 있으며, TLC 등을 통하여 출발물질인 상기 화학식 2로 표시되는 아릴 하이드로젠 포스페이트 유도체가 완전히 소모됨을 확인한 후 반응을 완결시킨다. 반응이 완결되면 추출과정 후 감압 하에서 용매를 증류시킨 후 메탄올 용매 하에 TMS-diazomethane [TMS : trimethylsilyl] 과 실온에서 30분간 반응시킨 후 용매를 증류시킨 후 관 크로마토그래피 등의 통상의 방법을 통하여 목적물을 분리 정제할 수 있다. The reaction time may vary depending on the kind of the reactant, the kind of the solvent and the amount of the solvent, and the reaction is completed after confirming that the starting material, the arylhydrogenphosphate derivative represented by the formula (2), is completely consumed through TLC or the like. When the reaction is completed, the solvent is distilled off under reduced pressure after the extraction, and the reaction is carried out with TMS-diazomethane [TMS: trimethylsilyl] in methanol for 30 minutes at room temperature. The solvent is then distilled off, And can be separated and purified.
이하, 실시예를 통하여 본 발명의 구성을 보다 구체적으로 설명하지만, 하기의 실시예들은 본 발명에 대한 이해를 돕기 위한 것으로서, 본 발명의 범위가 여기에 국한된 것은 아니다.Hereinafter, the structure of the present invention will be described in more detail with reference to examples. However, the following examples are provided to aid understanding of the present invention, and the scope of the present invention is not limited thereto.
[실시예 1] (E)-에틸 3-(2-((다이메톡시포스포릴)옥시)-3-메틸페닐)아크릴레이트 ((E)-ethyl 3-(2-((dimethoxyphosphoryl)oxy)-3-methylphenyl)-acrylate)의 제조
EXAMPLE 1 Synthesis of (E) -ethyl 3- (2 - ((dimethoxyphosphoryl) oxy) -3-methylphenyl) 3-methylphenyl) -acrylate
Glove box에서 반응용 v-바이알 (직경 : 2 cm, 높이 : 4 cm)에 Pd(OAc)2 (3.36 mg, 0.015mmol), AgOAc (75.1 mg, 0.45 mmol)를 넣고 methyl o-tolyl hydrogen phosphate (30.3 mg, 0.15 mmol), ethyl acrylate (30.0 mg, 0.3 mmol), 1,4-dioxane (1.0 mL)를 넣은 후 110 ℃에서 15 시간동안 교반하였다. TLC를 통하여 출발 물질이 완전히 사라짐을 확인한 후 1N 염산 (1 mL)을 사용하여 반응을 종결시켰다. 수용액 층을 EtOAc (3 mL × 3)로 씻어 주고, 추출한 유기층을 무수 MgSO4로 건조하여 여과하였다. 용매를 제거한 후 MeOH (0.5 mL)와 TMS-diazomethane [TMS : trimethylsilyl] (0.40 mL, 0.75 mmol, 2.0 M in hexane, 5.0 equiv)을 넣은 후 실온에서 30 분간 교반하였다. TLC를 통하여 출발 물질이 완전히 사라짐을 확인한 후 용매를 제거하였다. 관 크로마토그래피를 통하여 생성물인 (E)-ethyl 3-(2-((dimethoxyphosphoryl)oxy)-3-methylphenyl)-acrylate (37.7 mg, 80%)를 얻었다.Pd (OAc) 2 (3.36 mg, 0.015 mmol) and AgOAc (75.1 mg, 0.45 mmol) were added to a reaction v-vial (diameter: 2 cm, height: 4 cm) in a glove box and methyl o- toluyl hydrogen phosphate 30.3 mg, 0.15 mmol), ethyl acrylate (30.0 mg, 0.3 mmol) and 1,4-dioxane (1.0 mL) were added thereto, followed by stirring at 110 ° C for 15 hours. After confirming that the starting material disappeared completely through TLC, the reaction was terminated using 1N hydrochloric acid (1 mL). The aqueous layer was washed with EtOAc (3 mL × 3), and the extracted organic layer was dried over anhydrous MgSO 4 and filtered. After the solvent was removed, MeOH (0.5 mL) and TMS-diazomethane (TMS: trimethylsilyl) (0.40 mL, 0.75 mmol, 2.0 M in hexane, 5.0 equiv) were added and stirred at room temperature for 30 min. After confirming that the starting material completely disappeared through TLC, the solvent was removed. (E) -ethyl 3- (2 - ((dimethoxyphosphoryl) oxy) -3-methylphenyl) -acrylate (37.7 mg, 80%) was obtained through column chromatography.
1H NMR (400 MHz, CDCl3) δ 8.07 (d, J = 16.0 Hz, 1H), 7.46 (d, J = 7.4 Hz, 1H), 7.25 (d, J = 7.5 Hz, 1H), 7.12 (t, J = 7.8 Hz, 1H), 6.41 (d, J = 16.0 Hz, 1H), 4.26 (q, J = 7.1 Hz, 2H), 3.90 (d, J = 11.6 Hz, 6H), 2.41 (s, 3H), 1.34 (t, J = 7.1 Hz, 3H) 1 H NMR (400 MHz, CDCl 3) δ 8.07 (d, J = 16.0 Hz, 1H), 7.46 (d, J = 7.4 Hz, 1H), 7.25 (d, J = 7.5 Hz, 1H), 7.12 (t , J = 7.8 Hz, 1H) , 6.41 (d, J = 16.0 Hz, 1H), 4.26 (q, J = 7.1 Hz, 2H), 3.90 (d, J = 11.6 Hz, 6H), 2.41 (s, 3H ), 1.34 (t, J = 7.1 Hz, 3 H)
[실시예 2] (E)-에틸 3-(3-(터트-부틸)-2-((다이메톡시포스포릴)옥 시)페닐)아크릴레이트) ((E)-ethyl 3-(3-(tert-butyl)-2-((dimethoxyphospho -ryl)oxy)phenyl)acrylate)의 제조Example 2 Synthesis of (E) -ethyl 3- (3-tert-butyl) -2 - ((dimethoxyphosphoryl) oxy) ( tert- butyl) -2 - ((dimethoxyphospho-yl) oxy) phenyl) acrylate
Glove box에서 반응용 v-바이알 (직경 : 2 cm, 높이 : 4 cm)에 Pd(OAc)2 (3.36 mg, 0.015mmol), AgOAc (75.1 mg, 0.45 mmol)를 넣고 2-tert-butylphenyl methyl hydrogen phosphate (36.6 mg, 0.15 mmol), ethyl acrylate (30.0 mg, 0.3 mmol), 1,4-dioxane (1.0 mL)를 넣은 후 110 ℃에서 15 시간동안 교반하였다. TLC를 통하여 출발 물질이 완전히 사라짐을 확인한 후 1N 염산 (1 mL)을 사용하여 반응을 종결시켰다. 수용액 층을 EtOAc (3 mL × 3)로 씻어 주고, 추출한 유기층을 무수 MgSO4로 건조하여 여과하였다. 용매를 제거한 후 MeOH (0.5 mL)와 TMS-diazomethane (0.40 mL, 0.75 mmol, 2.0 M in hexane, 5.0 equiv)을 넣은 후 실온에서 30 분간 교반하였다. TLC를 통하여 출발 물질이 완전히 사라짐을 확인한 후 용매를 제거하였다. 관 크로마토그래피를 통하여 생성물인 (E)-ethyl 3-(3-(tert-butyl)-2-((dimethoxyphosphoryl)oxy)phenyl)acrylate (50.2 mg, 94%)를 얻었다.V- reaction vial for in Glove box (diameter: 2 cm, height: 4 cm) to Pd (OAc) 2 (3.36 mg , 0.015mmol), insert the AgOAc (75.1 mg, 0.45 mmol) 2- tert -butylphenyl methyl hydrogen phosphate (36.6 mg, 0.15 mmol), ethyl acrylate (30.0 mg, 0.3 mmol) and 1,4-dioxane (1.0 mL) were added thereto, followed by stirring at 110 ° C for 15 hours. After confirming that the starting material disappeared completely through TLC, the reaction was terminated using 1N hydrochloric acid (1 mL). The aqueous layer was washed with EtOAc (3 mL × 3), and the extracted organic layer was dried over anhydrous MgSO 4 and filtered. After removal of the solvent, MeOH (0.5 mL) and TMS-diazomethane (0.40 mL, 0.75 mmol, 2.0 M in hexane, 5.0 equiv) were added and stirred at room temperature for 30 min. After confirming that the starting material completely disappeared through TLC, the solvent was removed. The product, (E) -ethyl 3- ( tert- butyl) -2 - ((dimethoxyphosphoryl) oxy) phenyl) acrylate (50.2 mg, 94%) was obtained through column chromatography.
1H NMR (400 MHz, CDCl3) δ 8.16 (d, J = 15.9 Hz, 1H), 7.45 (d, J = 7.8 Hz, 2H), 7.16 -7.14 (m, 1H), 6.37 (d, J = 15.8 Hz, 1H), 4.27 (q, J = 7.1 Hz, 2H), 3.87 (d, J = 11.2 Hz, 6H), 1.45 (s, 9H), 1.34 (t, J = 7.1 Hz, 3H) 1 H NMR (400 MHz, CDCl 3) δ 8.16 (d, J = 15.9 Hz, 1H), 7.45 (d, J = 7.8 Hz, 2H), 7.16 -7.14 (m, 1H), 6.37 (d, J = 15.8 Hz, 1H), 4.27 ( q, J = 7.1 Hz, 2H), 3.87 (d, J = 11.2 Hz, 6H), 1.45 (s, 9H), 1.34 (t, J = 7.1 Hz, 3H)
[실시예 3] (E)-에틸 3-(3-벤질-2-((다이메톡시포스포릴)옥시)페닐) 아크릴레이트 ((E)-ethyl 3-(3-benzyl-2-((dimethoxyphosphoryl)oxy)pheny -l)acrylate)의 제조
Example 3 Synthesis of (E) -ethyl 3- (3-benzyl-2 - ((3-benzyl-2- dimethoxyphosphoryl) oxy) pheny-1) acrylate
Glove box에서 반응용 v-바이알 (직경 : 2 cm, 높이 : 4 cm)에 Pd(OAc)2 (3.36 mg, 0.015 mmol ), AgOAc (75.1 mg, 0.45 mmol)를 넣고 2-benzylphenyl methyl hydrogen phosphate (41.7 mg, 0.15 mmol), ethyl acrylate (30.0 mg, 0.3 mmol), 1,4-dioxane (1.0 mL)를 넣은 후 110 ℃에서 15 시간동안 교반하였다. TLC를 통하여 출발 물질이 완전히 사라짐을 확인한 후 1N 염산 (1 mL)을 사용하여 반응을 종결시켰다. 수용액 층을 EtOAc (3 mL × 3)로 씻어 주고, 추출한 유기층을 무수 MgSO4로 건조하여 여과하였다. 용매를 제거한 후 MeOH (0.5 mL)와 TMS-diazomethane (0.40 mL, 0.75 mmol, 2.0 M in hexane, 5.0 equiv)을 넣은 후 실온에서 30 분간 교반하였다. TLC를 통하여 출발 물질이 완전히 사라짐을 확인한 후 용매를 제거하였다. 관 크로마토그래피를 통하여 생성물인 (E)-ethyl 3-(3-benzyl-2-((dimethoxyphosphoryl)oxy)phenyl)acrylate (50.9 mg, 87%)를 얻었다.Pd (OAc) 2 (3.36 mg, 0.015 mmol) and AgOAc (75.1 mg, 0.45 mmol) were added to a reaction v-vial (diameter 2 cm, height 4 cm) in a glove box and 2-benzylphenyl methyl hydrogen phosphate 41.7 mg, 0.15 mmol), ethyl acrylate (30.0 mg, 0.3 mmol) and 1,4-dioxane (1.0 mL) were added thereto, followed by stirring at 110 ° C for 15 hours. After confirming that the starting material disappeared completely through TLC, the reaction was terminated using 1N hydrochloric acid (1 mL). The aqueous layer was washed with EtOAc (3 mL × 3), and the extracted organic layer was dried over anhydrous MgSO 4 and filtered. After removal of the solvent, MeOH (0.5 mL) and TMS-diazomethane (0.40 mL, 0.75 mmol, 2.0 M in hexane, 5.0 equiv) were added and stirred at room temperature for 30 min. After confirming that the starting material completely disappeared through TLC, the solvent was removed. The product, (E) -ethyl 3- (3-benzyl-2 - ((dimethoxyphosphoryl) oxy) phenyl) acrylate (50.9 mg, 87%) was obtained through column chromatography.
1H NMR (400 MHz, CDCl3) δ 8.09 (d, J = 16.0 Hz, 1H), 7.53 -7.46 (m, 1H), 7.34 -7.24 (m, 2H), 7.24 -7.17 (m, 3H), 7.15 - 7.00 (m, 2H), 6.42 (d, J = 16.0 Hz, 1H), 4.26 (q, J = 7.1 Hz, 2H), 4.18 (s, 2H), 3.85 (d, J = 11.4 Hz, 6H), 1.33 (t, J = 7.1 Hz, 3H) 1 H NMR (400 MHz, CDCl 3) δ 8.09 (d, J = 16.0 Hz, 1H), 7.53 -7.46 (m, 1H), 7.34 -7.24 (m, 2H), 7.24 -7.17 (m, 3H), 7.15 - 7.00 (m, 2H) , 6.42 (d, J = 16.0 Hz, 1H), 4.26 (q, J = 7.1 Hz, 2H), 4.18 (s, 2H), 3.85 (d, J = 11.4 Hz, 6H ), 1.33 (t, J = 7.1 Hz, 3 H)
[실시예 4] (E)-에틸 3-(2-((다이메톡시포스포릴)옥시)-3,4-다이메틸페닐)아크릴레이트 ((E)-ethyl 3-(2-((dimethoxyphosphoryl)oxy)-3,4-dimethylphenyl)acrylate)의 제조
Example 4 Synthesis of (E) -ethyl 3- (2 - ((dimethoxyphosphoryl) oxy) -3,4-dimethylphenyl) oxy) -3,4-dimethylphenyl) acrylate
Glove box에서 반응용 v-바이알 (직경 : 2 cm, 높이 : 4 cm)에 Pd(OAc)2 (3.36 mg, 0.015 mmol), AgOAc (75.1 mg, 0.45 mmol)를 넣고 2,3-dimethylphenyl methyl hydrogen phosphate (32.4 mg, 0.15 mmol), ethyl acrylate (30.0 mg, 0.3 mmol), 1,4-dioxane (1.0 mL)를 넣은 후 110 ℃에서 15 시간동안 교반하였다. TLC를 통하여 출발 물질이 완전히 사라짐을 확인한 후 1N 염산 (1 mL)을 사용하여 반응을 종결시켰다. 수용액 층을 EtOAc (3 mL × 3)로 씻어 주고, 추출한 유기층을 무수 MgSO4로 건조하여 여과하였다. 용매를 제거한 후 MeOH (0.5 mL)와 TMS-diazomethane (0.40 mL, 0.75 mmol, 2.0 M in hexane, 5.0 equiv)을 넣은 후 실온에서 30 분간 교반하였다. TLC를 통하여 출발 물질이 완전히 사라짐을 확인한 후 용매를 제거하였다. 관 크로마토그래피를 통하여 생성물인 (E)-ethyl 3-(2-((dimethoxyphosphoryl)oxy)-3,4-dimethylphenyl)acrylate (48.3 mg, 98%)를 얻었다.Pd (OAc) 2 (3.36 mg, 0.015 mmol) and AgOAc (75.1 mg, 0.45 mmol) were added to a reaction v-vial (diameter 2 cm, height 4 cm) phosphate (32.4 mg, 0.15 mmol), ethyl acrylate (30.0 mg, 0.3 mmol) and 1,4-dioxane (1.0 mL) were added thereto and stirred at 110 ° C for 15 hours. After confirming that the starting material disappeared completely through TLC, the reaction was terminated using 1N hydrochloric acid (1 mL). The aqueous layer was washed with EtOAc (3 mL × 3), and the extracted organic layer was dried over anhydrous MgSO 4 and filtered. After removal of the solvent, MeOH (0.5 mL) and TMS-diazomethane (0.40 mL, 0.75 mmol, 2.0 M in hexane, 5.0 equiv) were added and stirred at room temperature for 30 min. After confirming that the starting material completely disappeared through TLC, the solvent was removed. The product, (E) -ethyl 3- (2 - ((dimethoxyphosphoryl) oxy) -3,4-dimethylphenyl) acrylate (48.3 mg, 98%) was obtained through column chromatography.
1H NMR (400 MHz, CDCl3) δ 8.04 (d, J = 16.0 Hz, 1H), 7.37 (d, J = 8.0 Hz, 1H), 7.02 (d, J = 8.0 Hz, 1H), 6.38 (d, J = 16.0 Hz, 1H), 4.26 (q, J = 7.1 Hz, 2H), 3.89 (d, J = 11.3 Hz, 6H), 2.29 (d, J = 7.4 Hz, 3H), 1.33 (t, J = 7.1 Hz, 3H) 1 H NMR (400 MHz, CDCl 3) δ 8.04 (d, J = 16.0 Hz, 1H), 7.37 (d, J = 8.0 Hz, 1H), 7.02 (d, J = 8.0 Hz, 1H), 6.38 (d , J = 16.0 Hz, 1H) , 4.26 (q, J = 7.1 Hz, 2H), 3.89 (d, J = 11.3 Hz, 6H), 2.29 (d, J = 7.4 Hz, 3H), 1.33 (t, J = 7.1 Hz, 3H)
[실시예 5] (E)-에틸 3-(2-((다이메톡시포스포릴)옥시)-4-메틸페닐) 아크릴레이트 ((E)-ethyl 3-(2-((dimethoxyphosphoryl)oxy)-4-methylpheny -l) acrylate)의 제조[Example 5] (E) -ethyl 3- (2 - ((dimethoxyphosphoryl) oxy) -4-methylphenyl) acrylate 4-methylpheny-1) acrylate
Glove box에서 반응용 v-바이알 (직경 : 2 cm, 높이 : 4 cm)에 Pd(OAc)2 (3.36 mg, 0.015 mmol), AgOAc (75.1 mg, 0.45 mmol)를 넣고 methyl m-tolyl hydrogen phosphate (30.3 mg, 0.15 mmol), ethyl acrylate (30.0 mg, 0.3 mmol), 1,4-dioxane (1.0 mL)를 넣은 후 110 ℃에서 15 시간동안 교반하였다. TLC를 통하여 출발 물질이 완전히 사라짐을 확인한 후 1N 염산 (1 mL)을 사용하여 반응을 종결시켰다. 수용액 층을 EtOAc (3 mL × 3)로 씻어 주고, 추출한 유기층을 무수 MgSO4로 건조하여 여과하였다. 용매를 제거한 후 MeOH (0.5 mL)와 TMS-diazomethane (0.40 mL, 0.75 mmol, 2.0 M in hexane, 5.0 equiv)을 넣은 후 실온에서 30 분간 교반하였다. TLC를 통하여 출발 물질이 완전히 사라짐을 확인한 후 용매를 제거하였다. 관 크로마토그래피를 통하여 생성물인 (E)-ethyl 3-(2-((dimethoxyphosphoryl) -oxy)-4-methylphenyl) acrylate (38.2 mg, 81%)를 얻었다.Pd (OAc) 2 (3.36 mg, 0.015 mmol) and AgOAc (75.1 mg, 0.45 mmol) were added to a reaction v-vial (diameter: 2 cm, height: 4 cm) in a glove box and methyl m- toluyl hydrogen phosphate 30.3 mg, 0.15 mmol), ethyl acrylate (30.0 mg, 0.3 mmol) and 1,4-dioxane (1.0 mL) were added thereto, followed by stirring at 110 ° C for 15 hours. After confirming that the starting material disappeared completely through TLC, the reaction was terminated using 1N hydrochloric acid (1 mL). The aqueous layer was washed with EtOAc (3 mL × 3), and the extracted organic layer was dried over anhydrous MgSO 4 and filtered. After removal of the solvent, MeOH (0.5 mL) and TMS-diazomethane (0.40 mL, 0.75 mmol, 2.0 M in hexane, 5.0 equiv) were added and stirred at room temperature for 30 min. After confirming that the starting material completely disappeared through TLC, the solvent was removed. (E) -ethyl 3- (2 - ((dimethoxyphosphoryl) -oxy) -4-methylphenyl) acrylate (38.2 mg, 81%) was obtained through column chromatography.
1H NMR (400 MHz, CDCl3) δ7.95 (d, J = 16.1 Hz, 1H), 7.49 (d, J = 8.0 Hz, 1H), 7.22 (s, 1H), 7.01 (d, J = 8.0 Hz, 1H), 6.42 (d, J = 16.1 Hz, 1H), 4.26 (q, J = 7.1 Hz, 2H), 3.90 (d, J = 11.4 Hz, 6H), 2.37 (s, 3H), 1.33 (t, J = 7.1 Hz, 3H) 1 H NMR (400 MHz, CDCl 3) δ7.95 (d, J = 16.1 Hz, 1H), 7.49 (d, J = 8.0 Hz, 1H), 7.22 (s, 1H), 7.01 (d, J = 8.0 Hz, 1H), 6.42 (d , J = 16.1 Hz, 1H), 4.26 (q, J = 7.1 Hz, 2H), 3.90 (d, J = 11.4 Hz, 6H), 2.37 (s, 3H), 1.33 ( t, J = 7.1 Hz, 3H)
[실시예 6] (E)-에틸 3-(5-클로로-2-((다이메톡시포스포릴)옥시)-3-메틸페닐)아크릴레이트 ((E)-ethyl 3-(5-chloro-2-((dimethoxyphosphoryl) -oxy)-3-methylphenyl)acrylate)의 제조Example 6 Synthesis of (E) -ethyl 3- (5-chloro-2 - ((dimethoxyphosphoryl) oxy) -3-methylphenyl) acrylate - ((dimethoxyphosphoryl) -oxy) -3-methylphenyl) acrylate
Glove box에서 반응용 v-바이알 (직경 : 2 cm, 높이 : 4 cm)에 Pd(OAc)2 (3.36 mg, 0.015 mmol ), AgOAc (75.1 mg, 0.45 mmol)를 넣고 4-chloro-2-methylphenyl methyl hydrogen phosphate (35.5 mg, 0.15 mmol), ethyl acrylate (30.0 mg, 0.3 mmol), 1,4-dioxane (1.0 mL)를 넣은 후 110 ℃에서 15 시간동안 교반하였다. TLC를 통하여 출발 물질이 완전히 사라짐을 확인한 후 1N 염산 (1 mL)을 사용하여 반응을 종결시켰다. 수용액 층을 EtOAc (3 mL × 3)로 씻어 주고, 추출한 유기층을 무수 MgSO4로 건조하여 여과하였다. 용매를 제거한 후 MeOH (0.5 mL)와 TMS-diazomethane (0.40 mL, 0.75 mmol, 2.0 M in hexane, 5.0 equiv)을 넣은 후 실온에서 30 분간 교반하였다. TLC를 통하여 출발 물질이 완전히 사라짐을 확인한 후 용매를 제거하였다. 관 크로마토그래피를 통하여 생성물인 (E)-ethyl 3-(5-chloro-2-((dimethoxyphosphoryl)oxy)-3-methylphenyl)acrylate (39.8 mg, 76%)를 얻었다.Pd (OAc) 2 (3.36 mg, 0.015 mmol) and AgOAc (75.1 mg, 0.45 mmol) were added to a reaction v-vial (diameter: 2 cm, height: 4 cm) in a glove box and 4-chloro-2-methylphenyl methyl hydrogen phosphate (35.5 mg, 0.15 mmol), ethyl acrylate (30.0 mg, 0.3 mmol) and 1,4-dioxane (1.0 mL) were added thereto and stirred at 110 ° C for 15 hours. After confirming that the starting material disappeared completely through TLC, the reaction was terminated using 1N hydrochloric acid (1 mL). The aqueous layer was washed with EtOAc (3 mL × 3), and the extracted organic layer was dried over anhydrous MgSO 4 and filtered. After removal of the solvent, MeOH (0.5 mL) and TMS-diazomethane (0.40 mL, 0.75 mmol, 2.0 M in hexane, 5.0 equiv) were added and stirred at room temperature for 30 min. After confirming that the starting material completely disappeared through TLC, the solvent was removed. (E) -ethyl 3- (5-chloro-2- (dimethoxyphosphoryl) oxy) -3-methylphenyl) acrylate (39.8 mg, 76%) was obtained through column chromatography.
1H NMR (400 MHz, CDCl3): δ 7.97 (d, J = 16.0 Hz, 1H), 7.42 (d, J = 2.4 Hz, 1H), 7.22 (d, J = 1.9 Hz, 1H), 6.40 (d, J = 16.0 Hz,1H), 4.26 (q, J = 7.1 Hz, 2H), 3.89 (d, J = 11.6 Hz, 6H), 2.38 (s, 3H), 1.33 (t, J = 7.1 Hz, 3H) 1 H NMR (400 MHz, CDCl 3): δ 7.97 (d, J = 16.0 Hz, 1H), 7.42 (d, J = 2.4 Hz, 1H), 7.22 (d, J = 1.9 Hz, 1H), 6.40 ( d, J = 16.0 Hz, 1H ), 4.26 (q, J = 7.1 Hz, 2H), 3.89 (d, J = 11.6 Hz, 6H), 2.38 (s, 3H), 1.33 (t, J = 7.1 Hz, 3H)
[실시예 7] (E)-에틸 3-(3-아다만탄-1-일)-2-((다이메톡시포스포릴) 옥시)-5-메틸페닐)아크릴레이트 ((E)-ethyl 3-(3-(adamantan-1-yl)-2-((dimethoxyphosphoryl)oxy)-5-methylphenyl) acrylate)의 제조Example 7 Synthesis of (E) -ethyl 3- (3-adamantan-1-yl) -2 - ((dimethoxyphosphoryl) oxy) - (3- (adamantan-1-yl) -2 - ((dimethoxyphosphoryl) oxy) -5-methylphenyl) acrylate
Glove box에서 반응용 v-바이알 (직경 : 2 cm, 높이 : 4 cm)에 Pd(OAc)2 (3.36 mg, 0.015 mmol ), AgOAc (75.1 mg, 0.45 mmol)를 넣고 2-adamantyl-4-methylphenyl methyl hydrogen phosphate (50.5 mg, 0.15 mmol), ethyl acrylate (30.0 mg, 0.3 mmol), 1,4-dioxane (1.0 mL)를 넣은 후 110 ℃에서 15 시간동안 교반하였다. TLC를 통하여 출발 물질이 완전히 사라짐을 확인한 후 1N 염산 (1 mL)을 사용하여 반응을 종결시켰다. 수용액 층을 EtOAc (3 mL × 3)로 씻어 주고, 추출한 유기층을 무수 MgSO4로 건조하여 여과하였다. 용매를 제거한 후 MeOH (0.5 mL)와 TMS-diazomethane (0.40 mL, 0.75 mmol, 2.0 M in hexane, 5.0 equiv)을 넣은 후 실온에서 30 분간 교반하였다. TLC를 통하여 출발 물질이 완전히 사라짐을 확인한 후 용매를 제거하였다. 관 크로마토그래피를 통하여 생성물인 (E)-ethyl 3-(3-(adamantan-1-yl)-2-((dimethoxyphosphoryl)oxy)-5-methyl -phenyl)acrylate (64.6 mg, 96%)를 얻었다.Pd (OAc) 2 (3.36 mg, 0.015 mmol) and AgOAc (75.1 mg, 0.45 mmol) were added to a reaction v-vial (diameter 2 cm, height 4 cm) in a glove box and 2-adamantyl-4-methylphenyl methyl hydrogen phosphate (50.5 mg, 0.15 mmol), ethyl acrylate (30.0 mg, 0.3 mmol) and 1,4-dioxane (1.0 mL) were added thereto and stirred at 110 ° C for 15 hours. After confirming that the starting material disappeared completely through TLC, the reaction was terminated using 1N hydrochloric acid (1 mL). The aqueous layer was washed with EtOAc (3 mL × 3), and the extracted organic layer was dried over anhydrous MgSO 4 and filtered. After removal of the solvent, MeOH (0.5 mL) and TMS-diazomethane (0.40 mL, 0.75 mmol, 2.0 M in hexane, 5.0 equiv) were added and stirred at room temperature for 30 min. After confirming that the starting material completely disappeared through TLC, the solvent was removed. The product, (E) -ethyl 3- (3- (adamantan-1-yl) -2 - ((dimethoxyphosphoryl) oxy) -5-methyl-phenyl) acrylate (64.6 mg, 96% .
1H NMR (400 MHz, CDCl3): δ 8.13 (d, J = 15.8 Hz, 1H), 7.23 (s, 1H), 7.20 (s, 1H), 6.35 (d, J = 15.8 Hz, 1H), 4.26 (q, J = 7.1 Hz, 2H), 3.88 (d, J = 11.6 Hz, 6H), 2.31 (s, 3H), 2.11 (s, 9H), 1.84-1.72 (m, 6H), 1.33 (t, J = 7.1 Hz, 3H) 1 H NMR (400 MHz, CDCl 3): δ 8.13 (d, J = 15.8 Hz , 1H), 7.23 (s, 1H), 7.20 (s, 1H), 6.35 (d, J = 15.8 Hz, 1H), 4.26 (q, J = 7.1 Hz, 2H), (M, 6H), 1.33 (t, J = 7.1 Hz, 3H), 3.88 (d, J = 11.6 Hz, 6H), 2.31
[실시예 8] (E)-에틸 3-(4-(터트-부틸)-2-((다이메톡시포스포릴)옥시) 페닐)아크릴레이트 ((E)-ethyl 3-(4-(tert-butyl)-2-((dimethoxyphosphoryl) -oxy)phenyl)acrylate)의 제조[Example 8] (E) - ethyl 3- (4- (tert-butyl) -2 - ((dimethoxy-phosphoryl) oxy) phenyl) acrylate ((E) -ethyl 3- (4- (tert -butyl) -2 - ((dimethoxyphosphoryl) -oxy) phenyl) acrylate
Glove box에서 반응용 v-바이알 (직경 : 2 cm, 높이 : 4 cm)에 Pd(OAc)2 (3.36 mg, 0.015 mmol ), AgOAc (75.1 mg, 0.45 mmol)를 넣고 3-tert-butylphenyl methyl hydrogen phosphate (36.6 mg, 0.15 mmol), ethyl acrylate (30.0 mg, 0.3 mmol), 1,4-dioxane (1.0 mL)를 넣은 후 110 ℃에서 15 시간동안 교반하였다. TLC를 통하여 출발 물질이 완전히 사라짐을 확인한 후 1N 염산 (1 mL)을 사용하여 반응을 종결시켰다. 수용액 층을 EtOAc (3 mL × 3)로 씻어 주고, 추출한 유기층을 무수 MgSO4로 건조하여 여과하였다. 용매를 제거한 후 MeOH (0.5 mL)와 TMS-diazomethane (0.40 mL, 0.75 mmol, 2.0 M in hexane, 5.0 equiv)을 넣은 후 실온에서 30 분간 교반하였다. TLC를 통하여 출발 물질이 완전히 사라짐을 확인한 후 용매를 제거하였다. 관 크로마토그래피를 통하여 생성물인 (E)-ethyl 3-(4-(tert-butyl)-2-((dimethoxyphosphoryl)oxy)phenyl)acrylate (45.4 mg, 85%)를 얻었다.V- reaction vial for in Glove box (diameter: 2 cm, height: 4 cm) to Pd (OAc) 2 (3.36 mg , 0.015 mmol), AgOAc (75.1 mg, 0.45 mmol) into a 3- tert -butylphenyl methyl hydrogen phosphate (36.6 mg, 0.15 mmol), ethyl acrylate (30.0 mg, 0.3 mmol) and 1,4-dioxane (1.0 mL) were added thereto, followed by stirring at 110 ° C for 15 hours. After confirming that the starting material disappeared completely through TLC, the reaction was terminated using 1N hydrochloric acid (1 mL). The aqueous layer was washed with EtOAc (3 mL × 3), and the extracted organic layer was dried over anhydrous MgSO 4 and filtered. After removal of the solvent, MeOH (0.5 mL) and TMS-diazomethane (0.40 mL, 0.75 mmol, 2.0 M in hexane, 5.0 equiv) were added and stirred at room temperature for 30 min. After confirming that the starting material completely disappeared through TLC, the solvent was removed. (E) -ethyl 3- (4- ( tert- butyl) -2 - ((dimethoxyphosphoryl) oxy) phenyl) acrylate (45.4 mg, 85%) was obtained through column chromatography.
1H NMR (400 MHz, CDCl3): δ 7.96 (d, J = 16.1 Hz, 1H), 7.53 (d, J = 8.3 Hz, 1H), 7.40 (s, 1H), 7.22 (d, J = 8.0 Hz, 1H), 6.43 (d, J = 16.1 Hz, 1H), 4.26 (q, J = 7.1 Hz, 2H), 3.89 (d, J = 11.6 Hz, 6H), 1.34 -1.30 (m, 12H) 1 H NMR (400 MHz, CDCl 3): δ 7.96 (d, J = 16.1 Hz, 1H), 7.53 (d, J = 8.3 Hz, 1H), 7.40 (s, 1H), 7.22 (d, J = 8.0 Hz, 1H), 6.43 (d , J = 16.1 Hz, 1H), 4.26 (q, J = 7.1 Hz, 2H), 3.89 (d, J = 11.6 Hz, 6H), 1.34 -1.30 (m, 12H)
[실시예 9] (E)-에틸 3-(2-((다이메톡시포스포릴)옥시)-4-메톡시 페닐)아크릴레이트 ((E)-ethyl 3-(2-((dimethoxyphosphoryl)oxy)-4-methoxy -phenyl)acrylate)의 제조Example 9 Synthesis of (E) -ethyl 3- (2 - ((dimethoxyphosphoryl) oxy) -4-methoxyphenyl) acrylate ) -4-methoxy-phenyl) acrylate
Glove box에서 반응용 v-바이알 (직경 : 2 cm, 높이 : 4 cm)에 Pd(OAc)2 (3.36 mg, 0.015 mmol ), AgOAc (75.1 mg, 0.45 mmol)를 넣고 3-methoxyphenyl methyl hydrogen phosphate (32.7 mg, 0.15 mmol), ethyl acrylate (30.0 mg, 0.3 mmol), 1,4-dioxane (1.0 mL)를 넣은 후 110 ℃에서 15 시간동안 교반하였다. TLC를 통하여 출발 물질이 완전히 사라짐을 확인한 후 1N 염산 (1 mL)을 사용하여 반응을 종결시켰다. 수용액 층을 EtOAc (3 mL × 3)로 씻어 주고, 추출한 유기층을 무수 MgSO4로 건조하여 여과하였다. 용매를 제거한 후 MeOH (0.5 mL)와 TMS-diazomethane (0.40 mL, 0.75 mmol, 2.0 M in hexane, 5.0 equiv)을 넣은 후 실온에서 30 분간 교반하였다. TLC를 통하여 출발 물질이 완전히 사라짐을 확인한 후 용매를 제거하였다. 관 크로마토그래피를 통하여 생성물인 (E)-ethyl 3-(2-((dimethoxyphosphoryl)oxy)-4-methoxyphenyl)acrylate (38.6 mg, 78%)를 얻었다.Pd (OAc) 2 (3.36 mg, 0.015 mmol) and AgOAc (75.1 mg, 0.45 mmol) were added to a reaction v-vial (diameter 2 cm, height 4 cm) in a glove box and 3-methoxyphenyl methyl hydrogen phosphate 32.7 mg, 0.15 mmol), ethyl acrylate (30.0 mg, 0.3 mmol) and 1,4-dioxane (1.0 mL) were added thereto, followed by stirring at 110 ° C for 15 hours. After confirming that the starting material disappeared completely through TLC, the reaction was terminated using 1N hydrochloric acid (1 mL). The aqueous layer was washed with EtOAc (3 mL × 3), and the extracted organic layer was dried over anhydrous MgSO 4 and filtered. After removal of the solvent, MeOH (0.5 mL) and TMS-diazomethane (0.40 mL, 0.75 mmol, 2.0 M in hexane, 5.0 equiv) were added and stirred at room temperature for 30 min. After confirming that the starting material completely disappeared through TLC, the solvent was removed. The product, (E) -ethyl 3- (2 - ((dimethoxyphosphoryl) oxy) -4-methoxyphenyl) acrylate (38.6 mg, 78%) was obtained by column chromatography.
1H NMR (400 MHz, CDCl3): δ 7.92 (d, J = 16.1 Hz, 1H), 7.54 (d, J = 8.8 Hz, 1H), 6.97 (dd, J = 2.4, 1.0 Hz, 1H), 6.76 (dd, J = 8.8, 2.5 Hz, 1H), 6.35 (d, J = 16.0 Hz, 1H), 4.25 (q, J = 7.2 Hz, 2H), 3.90 (d, J = 11.2 Hz, 6H), 3.84 (s, 3H), 1.34 (t, J = 7.2 Hz, 3H) 1 H NMR (400 MHz, CDCl 3): δ 7.92 (d, J = 16.1 Hz , 1H), 7.54 (d, J = 8.8 Hz, 1H), 6.97 (dd, J = 2.4, 1.0 Hz, 1H), 6.76 (dd, J = 8.8, 2.5 Hz, 1H ), 6.35 (d, J = 16.0 Hz, 1H), 4.25 (q, J = 7.2 Hz, 2H), 3.90 (d, J = 11.2 Hz, 6H), 3.84 (s, 3H), 1.34 (t, J = 7.2 Hz, 3 H)
[실시예 10] (E)-에틸 3-(3-((다이메톡시포스포릴)옥시)-4,5-다이메톡시페닐)아크릴레이트 ((E)-ethyl 3-(2-((dimethoxyphosphoryl)oxy)-4,5-dimethoxyphenyl)acrylate)의 제조Example 10 Synthesis of (E) -ethyl 3- (2 - (((E) -ethyl 3- (3-methyl- dimethoxyphosphoryl) oxy) -4,5-dimethoxyphenyl) acrylate
Glove box에서 반응용 v-바이알 (직경 : 2 cm, 높이 : 4 cm)에 Pd(OAc)2 (3.36 mg, 0.015 mmol), AgOAc (75.1 mg, 0.45 mmol)를 넣고 3,4-dimethoxyphenyl methyl hydrogen phosphate (37.2 mg, 0.15 mmol), ethyl acrylate (30.0 mg, 0.3 mmol), 1,4-dioxane (1.0 mL)를 넣은 후 110 ℃에서 15 시간동안 교반하였다. TLC를 통하여 출발 물질이 완전히 사라짐을 확인한 후 1N 염산 (1 mL)을 사용하여 반응을 종결시켰다. 수용액 층을 EtOAc (3 mL × 3)로 씻어 주고, 추출한 유기층을 무수 MgSO4로 건조하여 여과하였다. 용매를 제거한 후 MeOH (0.5 mL)와 TMS-diazomethane (0.40 mL, 0.75 mmol, 2.0 M in hexane, 5.0 equiv)을 넣은 후 실온에서 30 분간 교반하였다. TLC를 통하여 출발 물질이 완전히 사라짐을 확인한 후 용매를 제거하였다. 관 크로마토그래피를 통하여 생성물인 (E)-ethyl 3-(2-((dimethoxyphosphoryl)oxy)-4,5-dimethoxyphenyl)acrylate (43.2 mg, 80%)를 얻었다.Pd (OAc) 2 (3.36 mg, 0.015 mmol) and AgOAc (75.1 mg, 0.45 mmol) were added to a reaction v-vial (diameter: 2 cm, height: 4 cm) in a glove box and 3,4-dimethoxyphenyl methyl hydrogen phosphate (37.2 mg, 0.15 mmol), ethyl acrylate (30.0 mg, 0.3 mmol) and 1,4-dioxane (1.0 mL) were added thereto and stirred at 110 ° C for 15 hours. After confirming that the starting material disappeared completely through TLC, the reaction was terminated using 1N hydrochloric acid (1 mL). The aqueous layer was washed with EtOAc (3 mL × 3), and the extracted organic layer was dried over anhydrous MgSO 4 and filtered. After removal of the solvent, MeOH (0.5 mL) and TMS-diazomethane (0.40 mL, 0.75 mmol, 2.0 M in hexane, 5.0 equiv) were added and stirred at room temperature for 30 min. After confirming that the starting material completely disappeared through TLC, the solvent was removed. (E) -ethyl 3- (2 - ((dimethoxyphosphoryl) oxy) -4,5-dimethoxyphenyl) acrylate (43.2 mg, 80%) was obtained through column chromatography.
1H NMR (400 MHz, CDCl3): δ 7.94 (d, J = 16.0 Hz, 1H), 7.03 (s, 1H), 6.97 (s, 1H), 6.34 (d, J = 16.0 Hz, 1H), 4.26 (q, J = 7.1 Hz, 2H), 3.92 (s, 3H), 3.90 (s, 3H), 3.89 (d, J = 6.0 Hz, 6H), 1.33 (t, J = 7.2 Hz, 3H) 1 H NMR (400 MHz, CDCl 3): δ 7.94 (d, J = 16.0 Hz , 1H), 7.03 (s, 1H), 6.97 (s, 1H), 6.34 (d, J = 16.0 Hz, 1H), 4.26 (q, J = 7.1 Hz, 2H), (S, 3H), 3.89 (d, J = 6.0 Hz, 6H), 1.33 (t, J = 7.2 Hz,
[실시예 11] (E)-에틸 3-(1-((다이메톡시포스포릴)옥시)나프탈렌-2-일)아크릴레이트 ((E)-ethyl 3-(1-((dimethoxyphosphoryl)oxy)naphthalen-2-yl)acrylate)의 제조Example 11 Synthesis of (E) -ethyl 3- (1 - ((dimethoxyphosphoryl) oxy) naphthalen-2-yl) naphthalen-2-yl) acrylate
Glove box에서 반응용 v-바이알 (직경 : 2 cm, 높이 : 4 cm)에 Pd(OAc)2 (3.36 mg, 0.015 mmol ), AgOAc (75.1 mg, 0.45 mmol)를 넣고 methyl naphthalen-1-yl hydrogen phosphate (35.7 mg, 0.15 mmol), ethyl acrylate (30.0 mg, 0.3 mmol), 1,4-dioxane (1.0 mL)를 넣은 후 110 ℃에서 15 시간동안 교반하였다. TLC를 통하여 출발 물질이 완전히 사라짐을 확인한 후 1N 염산 (1 mL)을 사용하여 반응을 종결시켰다. 수용액 층을 EtOAc (3 mL × 3)로 씻어 주고, 추출한 유기층을 무수 MgSO4로 건조하여 여과하였다. 용매를 제거한 후 MeOH (0.5 mL)와 TMS-diazomethane (0.40 mL, 0.75 mmol, 2.0 M in hexane, 5.0 equiv)을 넣은 후 실온에서 30 분간 교반하였다. TLC를 통하여 출발 물질이 완전히 사라짐을 확인한 후 용매를 제거하였다. 관 크로마토그래피를 통하여 생성물인 (E)-ethyl 3-(1-((dimethoxyphosphoryl)oxy)naphthalen-2-yl)acrylate (43.6 mg, 83%)를 얻었다. In a glove box, Pd (OAc) 2 (3.36 mg, 0.015 mmol) and AgOAc (75.1 mg, 0.45 mmol) were added to a reaction v-vial (diameter 2 cm, height 4 cm) and methyl naphthalen- phosphate (35.7 mg, 0.15 mmol), ethyl acrylate (30.0 mg, 0.3 mmol) and 1,4-dioxane (1.0 mL) were added thereto and stirred at 110 ° C for 15 hours. After confirming that the starting material disappeared completely through TLC, the reaction was terminated using 1N hydrochloric acid (1 mL). The aqueous layer was washed with EtOAc (3 mL × 3), and the extracted organic layer was dried over anhydrous MgSO 4 and filtered. After removal of the solvent, MeOH (0.5 mL) and TMS-diazomethane (0.40 mL, 0.75 mmol, 2.0 M in hexane, 5.0 equiv) were added and stirred at room temperature for 30 min. After confirming that the starting material completely disappeared through TLC, the solvent was removed. The product, (E) -ethyl 3- (1 - ((dimethoxyphosphoryl) oxy) naphthalen-2-yl) acrylate (43.6 mg, 83%) was obtained by column chromatography.
1H NMR (400 MHz, CDCl3): δ 8.33 - 8.24 (m, 2H), 7.82 (d, J = 8.0 Hz, 1H), 7.73-7.63 (m, 2H), 7.63-7.51 (m, 2H), 6.54 (d, J = 16.1 Hz, 1H), 4.29 (q, J = 7.1 Hz, 2H), 3.92 (d, J = 11.4 Hz, 6H), 1.36 (t, J = 7.1 Hz, 3H) 1 H NMR (400 MHz, CDCl 3): δ 8.33 - 8.24 (m, 2H) , 7.82 (d, J = 8.0 Hz, 1H), 7.73-7.63 (m, 2H), 7.63-7.51 (m, 2H), 6.54 (d, J = 16.1 Hz, 1H) , 4.29 (q, J = 7.1 Hz, 2H), 3.92 (d, J = 11.4 Hz, 6H), 1.36 (t, J = 7.1 Hz, 3H)
[실시예 12] (E)-에틸 3-(1-((다이메톡시포스포릴)옥시)-5,6,7,8-테트라하이드로나프탈렌-2-일)아크릴레이트 ((E)-ethyl 3-(1-((dimethoxy -phosphoryl)oxy)-5,6,7,8-tetrahydronaphthalen-2-yl) acrylate)의 제조Example 12 Synthesis of (E) -ethyl 3- (1 - ((dimethoxyphosphoryl) oxy) -5,6,7,8-tetrahydronaphthalen-2-yl) Preparation of 3- (1 - ((dimethoxy-phosphoryl) oxy) -5,6,7,8-tetrahydronaphthalen-2-yl) acrylate
Glove box에서 반응용 v-바이알 (직경 : 2 cm, 높이 : 4 cm)에 Pd(OAc)2 (3.36 mg, 0.015 mmol), AgOAc (75.1 mg, 0.45 mmol)를 넣고 methyl (5,6,7,8-tetrahydronaphthalen-1-yl) hydrogen phosphate (36.6 mg, 0.15 mmol), ethyl acrylate (30.0 mg, 0.3 mmol), 1,4-dioxane (1.0 mL)를 넣은 후 110 ℃에서 15 시간동안 교반하였다. TLC를 통하여 출발 물질이 완전히 사라짐을 확인한 후 1N 염산 (1 mL)을 사용하여 반응을 종결시켰다. 수용액 층을 EtOAc (3 mL × 3)로 씻어 주고, 추출한 유기층을 무수 MgSO4로 건조하여 여과하였다. 용매를 제거한 후 MeOH (0.5 mL)와 TMS-diazomethane (0.40 mL, 0.75 mmol, 2.0 M in hexane, 5.0 equiv)을 넣은 후 실온에서 30 분간 교반하였다. TLC를 통하여 출발 물질이 완전히 사라짐을 확인한 후 용매를 제거한다. 관 크로마토그래피를 통하여 생성물인 (E)-ethyl 3-(1-((dimethoxyphosphoryl)oxy)-5,6,7,8-tetrahydronaphthalen-2-yl) acrylate (42.5 mg, 80%)를 얻었다. Pd (OAc) 2 (3.36 mg, 0.015 mmol) and AgOAc (75.1 mg, 0.45 mmol) were added to a reaction v-vial (diameter 2 cm, height 4 cm) , 10-tetrahydronaphthalen-1-yl) hydrogenphosphate (36.6 mg, 0.15 mmol), ethyl acrylate (30.0 mg, 0.3 mmol) and 1,4-dioxane (1.0 mL) were added thereto and stirred at 110 ° C for 15 hours. After confirming that the starting material disappeared completely through TLC, the reaction was terminated using 1N hydrochloric acid (1 mL). The aqueous layer was washed with EtOAc (3 mL × 3), and the extracted organic layer was dried over anhydrous MgSO 4 and filtered. After removal of the solvent, MeOH (0.5 mL) and TMS-diazomethane (0.40 mL, 0.75 mmol, 2.0 M in hexane, 5.0 equiv) were added and stirred at room temperature for 30 min. After confirming that the starting material completely disappeared through TLC, the solvent is removed. (E) -ethyl 3- (1 - ((dimethoxyphosphoryl) oxy) -5,6,7,8-tetrahydronaphthalen-2-yl) acrylate (42.5 mg, 80%) was obtained through column chromatography.
1H NMR (400 MHz, CDCl3): δ 8.05 (d, J = 16.0 Hz, 1H), 7.36 (d, J = 8.1 Hz, 1H), 6.94 (d, J = 8.1 Hz, 1H), 6.37 (d, J = 16.0 Hz, 1H), 4.25 (q, J = 7.1 Hz, 2H), 3.89 (d, J = 11.4 Hz, 6H), 2.81 (dd, J = 26.7, 5.8 Hz, 4H), 1.87 -1.69 (m, 4H), 1.33 (t, J = 7.1 Hz, 3H) 1 H NMR (400 MHz, CDCl 3): δ 8.05 (d, J = 16.0 Hz, 1H), 7.36 (d, J = 8.1 Hz, 1H), 6.94 (d, J = 8.1 Hz, 1H), 6.37 ( d, J = 16.0 Hz, 1H ), 4.25 (q, J = 7.1 Hz, 2H), 3.89 (d, J = 11.4 Hz, 6H), 2.81 (dd, J = 26.7, 5.8 Hz, 4H), 1.87 - 1.69 (m, 4H), 1.33 (t, J = 7.1 Hz, 3H)
[실시예 13] (E)-에틸 3-(2-((다이메톡시포스포릴)옥시)-[1,1'-바 이페닐]-3-일)아크릴레이트 ((E)-ethyl 3-(2-((dimethoxyphosphoryl)oxy)-[1,1'-biphenyl]-3-yl)acrylate)의 제조Example 13 Synthesis of (E) -ethyl 3 - (2 - ((dimethoxyphosphoryl) oxy) - [1,1'-biphenyl] - (2 - ((dimethoxyphosphoryl) oxy) - [1,1'-biphenyl] -3-yl) acrylate
Glove box에서 반응용 v-바이알 (직경 : 2 cm, 높이 : 4 cm)에 Pd(OAc)2 (3.36 mg, 0.015 mmol ), AgOAc (75.1 mg, 0.45 mmol)를 넣고 [1,1`-biphenyl]-2-yl methyl hydrogen phosphate (39.6 mg, 0.15 mmol), ethyl acrylate (30.0 mg, 0.3 mmol), 1,4-dioxane (1.0 mL)를 넣은 후 110 ℃에서 15 시간동안 교반하였다. TLC를 통하여 출발 물질이 완전히 사라짐을 확인한 후 1N 염산 (1 mL)을 사용하여 반응을 종결시켰다. 수용액 층을 EtOAc (3 mL × 3)로 씻어 주고, 추출한 유기층을 무수 MgSO4로 건조하여 여과하였다. 용매를 제거한 후 MeOH (0.5 mL)와 TMS-diazomethane (0.40 mL, 0.75 mmol, 2.0 M in hexane, 5.0 equiv)을 넣은 후 실온에서 30 분간 교반하였다. TLC를 통하여 출발 물질이 완전히 사라짐을 확인한 후 용매를 제거한다. 관 크로마토그래피를 통하여 생성물인 (E)-ethyl 3-(2-((dimethoxyphosphoryl)oxy)-[1,1'-biphenyl]-3-yl)acrylate (37.3 mg, 66%)를 얻었다.Pd (OAc) 2 (3.36 mg, 0.015 mmol) and AgOAc (75.1 mg, 0.45 mmol) were added to a reaction v-vial (diameter: 2 cm, height: 4 cm) ] -2-yl methyl hydrogenphosphate (39.6 mg, 0.15 mmol), ethyl acrylate (30.0 mg, 0.3 mmol) and 1,4-dioxane (1.0 mL) were added thereto and stirred at 110 ° C for 15 hours. After confirming that the starting material disappeared completely through TLC, the reaction was terminated using 1N hydrochloric acid (1 mL). The aqueous layer was washed with EtOAc (3 mL × 3), and the extracted organic layer was dried over anhydrous MgSO 4 and filtered. After removal of the solvent, MeOH (0.5 mL) and TMS-diazomethane (0.40 mL, 0.75 mmol, 2.0 M in hexane, 5.0 equiv) were added and stirred at room temperature for 30 min. After confirming that the starting material completely disappeared through TLC, the solvent is removed. (E) -ethyl 3- (2 - ((dimethoxyphosphoryl) oxy) - [1,1'-biphenyl] -3-yl) acrylate (37.3 mg, 66%) was obtained through column chromatography.
1H NMR (400 MHz, CDCl3): δ 8.13 (d, J = 16.0 Hz, 1H, 7.62 (d, J = 7.8 Hz, 1H), 7.53-7.47 (m, 2H), 7.44 (t, J = 7.5 Hz, 2H), 7.40-7.32 (m, 2H), 7.31 -7.23 (m, 1H), 6.47 (d, J = 16.0 Hz, 1H), 4.27 (q, J = 7.1 Hz, 2H), 3.44 (d, J = 11.5 Hz, 6H), 1.34 (t, J = 7.1 Hz, 3H) 1 H NMR (400 MHz, CDCl 3): δ 8.13 (d, J = 16.0 Hz , 1H, 7.62 (d, J = 7.8 Hz, 1H), 7.53-7.47 (m, 2H), 7.44 (t, J = 7.5 Hz, 2H), 7.40-7.32 (m, 2H), 7.31 -7.23 (m, 1H), 6.47 (d, J = 16.0 Hz, 1H), 4.27 (q, J = 7.1 Hz, 2H), 3.44 (d, J = 11.5 Hz, 6H), 1.34 ( t, J = 7.1 Hz, 3H)
[실시예 14] (E)-에틸 3-(2-((다이메톡시포스포릴)옥시)페닐)아크릴 레이트 ((E)-ethyl 3-(2-((dimethoxyphosphoryl)oxy)phenyl)acrylate)의 제조EXAMPLE 14 Synthesis of (E) -ethyl 3- (2 - ((dimethoxyphosphoryl) oxy) phenyl) acrylate (E) Manufacturing
Glove box에서 반응용 v-바이알 (직경 : 2 cm, 높이 : 4 cm)에 Pd(OAc)2 (3.36 mg, 0.015 mmol ), AgOAc (75.1 mg, 0.45 mmol)를 넣고 methyl phenyl hydrogen phosphate (28.2 mg, 0.15 mmol), ethyl acrylate (18.0 mg, 0.18 mmol), 1,4-dioxane (1.0 mL)를 넣은 후 110 ℃에서 15 시간동안 교반하였다. TLC를 통하여 출발 물질이 완전히 사라짐을 확인한 후 1N 염산 (1 mL)을 사용하여 반응을 종결시켰다. 수용액 층을 EtOAc (3 mL × 3)로 씻어 주고, 추출한 유기층을 무수 MgSO4로 건조하여 여과하였다. 용매를 제거한 후 MeOH (0.5 mL)와 TMS-diazomethane (0.40 mL, 0.75 mmol, 2.0 M in hexane, 5.0 equiv)을 넣은 후 실온에서 30 분간 교반한다. TLC를 통하여 출발 물질이 완전히 사라짐을 확인한 후 용매를 제거하였다. 관 크로마토그래피를 통하여 생성물인 (E)-ethyl 3-(2-((dimethoxyphosphoryl) -oxy)phenyl)acrylate (24.8 mg, 55%)를 얻었다.Pd (OAc) 2 (3.36 mg, 0.015 mmol) and AgOAc (75.1 mg, 0.45 mmol) were added to a reaction v-vial (diameter: 2 cm, height: 4 cm) , 0.15 mmol), ethyl acrylate (18.0 mg, 0.18 mmol) and 1,4-dioxane (1.0 mL) were added thereto, followed by stirring at 110 ° C for 15 hours. After confirming that the starting material disappeared completely through TLC, the reaction was terminated using 1N hydrochloric acid (1 mL). The aqueous layer was washed with EtOAc (3 mL × 3), and the extracted organic layer was dried over anhydrous MgSO 4 and filtered. After removing the solvent, add MeOH (0.5 mL) and TMS-diazomethane (0.40 mL, 0.75 mmol, 2.0 M in hexane, 5.0 equiv) and stir at room temperature for 30 minutes. After confirming that the starting material completely disappeared through TLC, the solvent was removed. (E) -ethyl 3- (2 - ((dimethoxyphosphoryl) -oxy) phenyl) acrylate (24.8 mg, 55%) was obtained through column chromatography.
1H NMR (400 MHz, CDCl3): δ 7.99 (d, J = 16.1 Hz, 1H), 7.61 (d, J = 7.8 Hz, 1H), 7.45 - 7.32 (m, 2H), 7.21 (t, J = 7.4 Hz, 1H), 6.47 (d, J = 16.0 Hz, 1H), 4.27 (q, J = 7.1 Hz, 2H), 3.90 (d, J = 11.4 Hz, 6H), 1.34 (t, J = 7.1 Hz, 3H) 1 H NMR (400 MHz, CDCl 3): δ 7.99 (d, J = 16.1 Hz, 1H), 7.61 (d, J = 7.8 Hz, 1H), 7.45 - 7.32 (m, 2H), 7.21 (t, J = 7.4 Hz, 1H), 6.47 (d, J = 16.0 Hz, 1H), 4.27 (q, J = 7.1 Hz, 2H), 3.90 (d, J = 11.4 Hz, 6H), 1.34 (t, J = 7.1 Hz, 3H)
[실시예 15] (E)-에틸 3-(2-((다이메톡시포스포릴)옥시)-3-플로로페닐)아크릴레이트 ((E)-ethyl 3-(2-((dimethoxyphosphoryl)oxy)-3-fluorophenyl)acrylate)의 제조Example 15 Synthesis of (E) -ethyl 3- (2 - ((dimethoxyphosphoryl) oxy) -3-fluorophenyl) acrylate ) -3-fluorophenyl) acrylate
Glove box에서 반응용 v-바이알 (직경 : 2 cm, 높이 : 4 cm)에 Pd(OAc)2 (3.36 mg, 0.015 mmol ), AgOAc (75.1 mg, 0.45 mmol)를 넣고 2-fluorophenyl methyl hydrogen phosphate (30.9 mg, 0.15 mmol), ethyl acrylate (30.0 mg, 0.3 mmol), 1,4-dioxane (1.0 mL)를 넣은 후 110 ℃에서 15 시간동안 교반하였다. TLC를 통하여 출발 물질이 완전히 사라짐을 확인한 후 1N 염산 (1 mL)을 사용하여 반응을 종결시켰다. 수용액 층을 EtOAc (3 mL × 3)로 씻어 주고, 추출한 유기층을 무수 MgSO4로 건조하여 여과한다. 용매를 제거한 후 MeOH (0.5 mL)와 TMS-diazomethane (0.40 mL, 0.75 mmol, 2.0 M in hexane, 5.0 equiv)을 넣은 후 실온에서 30 분간 교반하였다. TLC를 통하여 출발 물질이 완전히 사라짐을 확인한 후 용매를 제거한다. 관 크로마토그래피를 통하여 생성물인 (E)-ethyl 3-(2-((dimethoxyphosphoryl)oxy)-3-fluorophenyl)acrylate (23.4 mg, 49%)를 얻었다.Pd (OAc) 2 (3.36 mg, 0.015 mmol) and AgOAc (75.1 mg, 0.45 mmol) were added to a reaction v-vial (diameter: 2 cm, height: 4 cm) in a glove box, and 2-fluorophenyl methyl hydrogen phosphate 30.9 mg, 0.15 mmol), ethyl acrylate (30.0 mg, 0.3 mmol) and 1,4-dioxane (1.0 mL) were added thereto, followed by stirring at 110 ° C for 15 hours. After confirming that the starting material disappeared completely through TLC, the reaction was terminated using 1N hydrochloric acid (1 mL). The aqueous layer was washed with EtOAc (3 mL × 3), and the extracted organic layer was dried over anhydrous MgSO 4 and filtered. After removal of the solvent, MeOH (0.5 mL) and TMS-diazomethane (0.40 mL, 0.75 mmol, 2.0 M in hexane, 5.0 equiv) were added and stirred at room temperature for 30 min. After confirming that the starting material completely disappeared through TLC, the solvent is removed. (E) -ethyl 3- (2 - ((dimethoxyphosphoryl) oxy) -3-fluorophenyl) acrylate (23.4 mg, 49%) was obtained through column chromatography.
1H NMR (400 MHz, CDCl3): δ 7.98 (d, J = 16.1 Hz, 1H), 7.47 - 7.34 (m, 1H), 7.25 - 7.09 (m, 2H), 6.47 (d, J = 16.1 Hz, 1H), 4.27 (q, J = 7.1 Hz, 2H), 3.96 (d, J = 11.5 Hz, 6H), 1.34 (t, J = 7.1 Hz, 3H) 1 H NMR (400 MHz, CDCl 3): δ 7.98 (d, J = 16.1 Hz, 1H), 7.47 - 7.34 (m, 1H), 7.25 - 7.09 (m, 2H), 6.47 (d, J = 16.1 Hz , 1H), 4.27 (q, J = 7.1 Hz, 2H), 3.96 (d, J = 11.5 Hz, 6H), 1.34 (t, J = 7.1 Hz, 3H)
[실시예 16] (E)-벤질 3-(2-((다이메톡시포스포릴)옥시)-3,4-다이메틸페닐)아크릴레이트 ((E)-benzyl 3-(2-((dimethoxyphosphoryl)oxy)-3,4-dimethylphenyl)acrylate)의 제조Example 16 Synthesis of (E) -benzyl 3- (2 - ((dimethoxyphosphoryl) oxy) -3,4-dimethylphenyl) oxy) -3,4-dimethylphenyl) acrylate
Glove box에서 반응용 v-바이알 (직경 : 2 cm, 높이 : 4 cm)에 Pd(OAc)2 (3.36 mg, 0.015 mmol ), AgOAc (75.1 mg, 0.45 mmol)를 넣고 2,3-dimethylphenyl methyl hydrogen phosphate (32.4 mg, 0.15 mmol), benzyl acrylate (48.7 mg, 0.3 mmol), 1,4-dioxane (1.0 mL)를 넣은 후 110 ℃에서 15 시간동안 교반하였다. TLC를 통하여 출발 물질이 완전히 사라짐을 확인한 후 1N 염산 (1 mL)을 사용하여 반응을 종결시켰다. 수용액 층을 EtOAc (3 mL × 3)로 씻어 주고, 추출한 유기층을 무수 MgSO4로 건조하여 여과하였다. 용매를 제거한 후 MeOH (0.5 mL)와 TMS-diazomethane (0.40 mL, 0.75 mmol, 2.0 M in hexane, 5.0 equiv)을 넣은 후 실온에서 30 분간 교반하였다. TLC를 통하여 출발 물질이 완전히 사라짐을 확인한 후 용매를 제거하였다. 관 크로마토그래피를 통하여 생성물인 (E)-benzyl 3-(2-((dimethoxyphosphoryl)oxy)-3,4-dimethylphenyl)acrylate (53. 3 mg, 91%)를 얻었다.Pd (OAc) 2 (3.36 mg, 0.015 mmol) and AgOAc (75.1 mg, 0.45 mmol) were added to a reaction v-vial (diameter 2 cm, height 4 cm) in a glove box and 2,3-dimethylphenyl methyl hydrogen phosphate (32.4 mg, 0.15 mmol), benzyl acrylate (48.7 mg, 0.3 mmol) and 1,4-dioxane (1.0 mL) were added thereto and stirred at 110 ° C for 15 hours. After confirming that the starting material disappeared completely through TLC, the reaction was terminated using 1N hydrochloric acid (1 mL). The aqueous layer was washed with EtOAc (3 mL × 3), and the extracted organic layer was dried over anhydrous MgSO 4 and filtered. After removal of the solvent, MeOH (0.5 mL) and TMS-diazomethane (0.40 mL, 0.75 mmol, 2.0 M in hexane, 5.0 equiv) were added and stirred at room temperature for 30 min. After confirming that the starting material completely disappeared through TLC, the solvent was removed. The product, (E) -benzyl 3- (2 - ((dimethoxyphosphoryl) oxy) -3,4-dimethylphenyl) acrylate (53.3 mg, 91%) was obtained by column chromatography.
1H NMR (400 MHz, CDCl3): δ 8.08 (d, J = 16.0 Hz, 3H), 7.49 - 7.29 (m, 6H), 7.01 (d, J = 8.0 Hz, 1H), 6.42 (d, J = 16.0 Hz, 1H), 5.24 (s, 2H), 3.80 (d, J = 11.4 Hz, 6H), 2.29 (s, 3H)1H NMR (400 MHz, CDCl3) : δ 8.08 (d, J = 16.0 Hz, 3H), 7.49 - 7.29 (m, 6H), 7.01 (d, J = 8.0 Hz, 1H), 6.42 (d, J = 16.0 2H), 3.80 (d, J = 11.4 Hz, 6H), 2.29 (s, 3H)
[실시예 17] (E)-2,3-다이메틸-6-(2-(페닐썰포닐)바이닐)페닐 다이메틸 포스페이트 ((E)-2,3-dimethyl-6-(2-(phenylsulfonyl)vinyl)phenyl dimethyl phosphate)의 제조[Example 17] (E) -2,3-dimethyl-6- (2- (phenylsulfonyl) vinyl) phenyldimethylphosphate ) vinyl) phenyl dimethyl phosphate
Glove box에서 반응용 v-바이알 (직경 : 2 cm, 높이 : 4 cm)에 Pd(OAc)2 (3.36 mg, 0.015 mmol ), AgOAc (75.1 mg, 0.45 mmol)를 넣고 2,3-dimethylphenyl methyl hydrogen phosphate (32.4 mg, 0.15 mmol), phenyl vinyl sulfone (50.5 mg, 0.3 mmol), 1,4-dioxane (1.0 mL)를 넣은 후 110 ℃에서 15 시간동안 교반하였다. TLC를 통하여 출발 물질이 완전히 사라짐을 확인한 후 1N 염산 (1 mL)을 사용하여 반응을 종결시켰다. 수용액 층을 EtOAc (3 mL × 3)로 씻어 주고, 추출한 유기층을 무수 MgSO4로 건조하여 여과하였다. 용매를 제거한 후 MeOH (0.5 mL)와 TMS-diazomethane (0.40 mL, 0.75 mmol, 2.0 M in hexane, 5.0 equiv)을 넣은 후 실온에서 30 분간 교반하였다. TLC를 통하여 출발 물질이 완전히 사라짐을 확인한 후 용매를 제거하였다. 관 크로마토그래피를 통하여 생성물인 (E)-2,3-dimethyl-6-(2-(phenylsulfonyl)vinyl)phenyl dimethyl phosphate (45.8 mg, 77%)를 얻었다.Pd (OAc) 2 (3.36 mg, 0.015 mmol) and AgOAc (75.1 mg, 0.45 mmol) were added to a reaction v-vial (diameter 2 cm, height 4 cm) in a glove box and 2,3-dimethylphenyl methyl hydrogen phosphate (32.4 mg, 0.15 mmol), phenyl vinyl sulfone (50.5 mg, 0.3 mmol) and 1,4-dioxane (1.0 mL) were added thereto and stirred at 110 ° C for 15 hours. After confirming that the starting material disappeared completely through TLC, the reaction was terminated using 1N hydrochloric acid (1 mL). The aqueous layer was washed with EtOAc (3 mL × 3), and the extracted organic layer was dried over anhydrous MgSO 4 and filtered. After removal of the solvent, MeOH (0.5 mL) and TMS-diazomethane (0.40 mL, 0.75 mmol, 2.0 M in hexane, 5.0 equiv) were added and stirred at room temperature for 30 min. After confirming that the starting material completely disappeared through TLC, the solvent was removed. (E) -2,3-dimethyl-6- (2- (phenylsulfonyl) vinyl) phenyldimethyl phosphate (45.8 mg, 77%) was obtained through column chromatography.
1H NMR (400 MHz, CDCl3): δ 8.04 (d, J = 15.4 Hz, 1H), 8.00 - 7.93 (m, 2H), 7.64 - 7.58 (m, 1H), 7.58 - 7.51 (m, 2H), 7.29 - 7.22 (m, 1H), 7.00 (d, J = 8.0 Hz, 1H), 6.81 (d, J = 15.4 Hz, 1H), 3.89 (d, J = 11.4 Hz, 6H), 2.30 (s, 3H), 2.29 (s, 3H) 1 H NMR (400 MHz, CDCl 3): δ 8.04 (d, J = 15.4 Hz, 1H), 8.00 - 7.93 (m, 2H), 7.64 - 7.58 (m, 1H), 7.58 - 7.51 (m, 2H) , 7.29 - 7.22 (m, 1H ), 7.00 (d, J = 8.0 Hz, 1H), 6.81 (d, J = 15.4 Hz, 1H), 3.89 (d, J = 11.4 Hz, 6H), 2.30 (s, 3H), 2.29 (s, 3H)
[실시예 18] (E)-6-(2-(다이에톡시포스포릴)바이닐)-2,3-다이메틸 페닐 다이메틸 포스페이트 ((E)-6-(2-(diethoxyphosphoryl)vinyl)-2,3-dimethylphenyl dimethyl phosphate)의 제조[Example 18] (E) -6- (2- (diethoxyphosphoryl) vinyl) -2,3-dimethylphenyl dimethyl phosphate ((E) 2,3-dimethylphenyl dimethyl phosphate
Glove box에서 반응용 v-바이알 (직경 : 2 cm, 높이 : 4 cm)에 Pd(OAc)2 (3.36 mg, 0.015 mmol), AgOAc (75.1 mg, 0.45 mmol)를 넣고 2,3-dimethylphenyl methyl hydrogen phosphate (32.4 mg, 0.15 mmol), diethyl vinylphosphonate (49.2 mg, 0.3 mmol), 1,4-dioxane (1.0 mL)를 넣은 후 110 ℃에서 15 시간동안 교반하였다. TLC를 통하여 출발 물질이 완전히 사라짐을 확인한 후 1N 염산 (1 mL)을 사용하여 반응을 종결시켰다. 수용액 층을 EtOAc (3 mL × 3)로 씻어 주고, 추출한 유기층을 무수 MgSO4로 건조하여 여과하였다. 용매를 제거한 후 MeOH (0.5 mL)와 TMS-diazomethane (0.40 mL, 0.75 mmol, 2.0 M in hexane, 5.0 equiv)을 넣은 후 실온에서 30 분간 교반하였다. TLC를 통하여 출발 물질이 완전히 사라짐을 확인한 후 용매를 제거하였다. 관 크로마토그래피를 통하여 생성물인 (E)-6-(2-(diethoxyphosphoryl)vinyl)-2,3-dimethylphenyl dimethyl phosphate (45.9 mg, 78%)를 얻었다.Pd (OAc) 2 (3.36 mg, 0.015 mmol) and AgOAc (75.1 mg, 0.45 mmol) were added to a reaction v-vial (diameter 2 cm, height 4 cm) in a glove box and 2,3-dimethylphenyl methyl hydrogen phosphate (32.4 mg, 0.15 mmol), diethyl vinylphosphonate (49.2 mg, 0.3 mmol) and 1,4-dioxane (1.0 mL) were added thereto and stirred at 110 ° C for 15 hours. After confirming that the starting material disappeared completely through TLC, the reaction was terminated using 1N hydrochloric acid (1 mL). The aqueous layer was washed with EtOAc (3 mL × 3), and the extracted organic layer was dried over anhydrous MgSO 4 and filtered. After removal of the solvent, MeOH (0.5 mL) and TMS-diazomethane (0.40 mL, 0.75 mmol, 2.0 M in hexane, 5.0 equiv) were added and stirred at room temperature for 30 min. After confirming that the starting material completely disappeared through TLC, the solvent was removed. (E) -6- (2- (diethoxyphosphoryl) vinyl) -2,3-dimethylphenyl dimethylphosphate (45.9 mg, 78%) was obtained through column chromatography.
1H NMR (400 MHz, CDCl3): δ 7.81 (dd, J = 22.7, 17.7 Hz, 1H), 7.34 (d, J = 7.9 Hz, 1H), 7.02 (d, J = 7.9 Hz, 1H), 6.20 (t, J = 18.1 Hz, 1H), 4.14 (dq, J = 14.0, 7.1 Hz, 4H), 3.89 (dd, J = 11.3, 1.3 Hz, 6H), 2.30 (s, 3H), 2.28 (s, 3H), 1.36 (t, J = 7.1 Hz, 3H), 1.35 (t, J = 7.0 Hz, 3H) 1 H NMR (400 MHz, CDCl 3): δ 7.81 (dd, J = 22.7, 17.7 Hz, 1H), 7.34 (d, J = 7.9 Hz, 1H), 7.02 (d, J = 7.9 Hz, 1H), 6.20 (t, J = 18.1 Hz , 1H), 4.14 (dq, J = 14.0, 7.1 Hz, 4H), 3.89 (dd, J = 11.3, 1.3 Hz, 6H), 2.30 (s, 3H), 2.28 (s , 3H), 1.36 (t, J = 7.1 Hz, 3H), 1.35 (t, J = 7.0 Hz, 3H)
[실시예 19] (E)-2,3-다이메틸-6-스타이릴페닐 다이메틸 포스페이트 ((E)-2,3-dimethyl-6-styrylphenyl dimethyl phosphate)의 제조Example 19 Preparation of (E) -2,3-dimethyl-6-styrylphenyldimethylphosphate ((E) -2,3-dimethyl-6-styrylphenyl dimethylphosphate)
Glove box에서 반응용 v-바이알 (직경 : 2 cm, 높이 : 4 cm)에 Pd(OAc)2 (3.36 mg, 0.015 mmol ), AgOAc (75.1 mg, 0.45 mmol)를 넣고 2,3-dimethylphenyl methyl hydrogen phosphate (32.4 mg, 0.15 mmol), styrene (31.2 mg, 0.3 mmol), 1,4-dioxane (1.0 mL)를 넣은 후 110 ℃에서 15 시간동안 교반하였다. TLC를 통하여 출발 물질이 완전히 사라짐을 확인한 후 1N 염산 (1 mL)을 사용하여 반응을 종결시켰다. 수용액 층을 EtOAc (3 mL × 3)로 씻어 주고, 추출한 유기층을 무수 MgSO4로 건조하여 여과하였다. 용매를 제거한 후 MeOH (0.5 mL)와 TMS-diazomethane (0.40 mL, 0.75 mmol, 2.0 M in hexane, 5.0 equiv)을 넣은 후 실온에서 30 분간 교반하였다. TLC를 통하여 출발 물질이 완전히 사라짐을 확인한 후 용매를 제거하였다. 관 크로마토그래피를 통하여 생성물인 (E)-2,3-dimethyl-6-styrylphenyl dimethyl phosphate (40.4 mg, 81%)를 얻었다.Pd (OAc) 2 (3.36 mg, 0.015 mmol) and AgOAc (75.1 mg, 0.45 mmol) were added to a reaction v-vial (diameter 2 cm, height 4 cm) in a glove box and 2,3-dimethylphenyl methyl hydrogen phosphate (32.4 mg, 0.15 mmol), styrene (31.2 mg, 0.3 mmol) and 1,4-dioxane (1.0 mL) were added and the mixture was stirred at 110 ° C for 15 hours. After confirming that the starting material disappeared completely through TLC, the reaction was terminated using 1N hydrochloric acid (1 mL). The aqueous layer was washed with EtOAc (3 mL × 3), and the extracted organic layer was dried over anhydrous MgSO 4 and filtered. After removal of the solvent, MeOH (0.5 mL) and TMS-diazomethane (0.40 mL, 0.75 mmol, 2.0 M in hexane, 5.0 equiv) were added and stirred at room temperature for 30 min. After confirming that the starting material completely disappeared through TLC, the solvent was removed. (E) -2,3-dimethyl-6-styrylphenyl dimethylphosphate (40.4 mg, 81%) was obtained through column chromatography.
1H NMR (400 MHz, CDCl3): δ 7.57 - 7.46 (m, 3H), 7.43 (d, J = 8.0 Hz, 1H), 7.35 (t, J = 7.6 Hz, 2H), 7.29 - 7.22 (m, 1H), 7.08 - 6.97 (m, 2H), 3.83 (d, J = 11.3 Hz, 6H), 2.30 (s, 3H), 2.29 (s, 3H) 1 H NMR (400 MHz, CDCl 3): δ 7.57 - 7.46 (m, 3H), 7.43 (d, J = 8.0 Hz, 1H), 7.35 (t, J = 7.6 Hz, 2H), 7.29 - 7.22 (m 2H), 3.83 (d, J = 11.3 Hz, 6H), 2.30 (s, 3H), 2.29 (s,
[실시예 20] (E)-2,3-다이메틸-6-(2-(퍼플로로페닐)바이닐)페닐 다이메틸 포스페이트 ((E)-2,3-dimethyl-6-(2-(perfluorophenyl)vinyl)phenyl dimethyl phosphate)의 제조Example 20 Synthesis of (E) -2,3-dimethyl-6- (2- ((E) -2,3-dimethyl- perfluorophenyl) vinyl) phenyl dimethyl phosphate
Glove box에서 반응용 v-바이알 (직경 : 2 cm, 높이 : 4 cm)에 Pd(OAc)2 (3.36 mg, 0.015 mmol), AgOAc (75.1 mg, 0.45 mmol)를 넣고 2,3-dimethylphenyl methyl hydrogen phosphate (32.4 mg, 0.15 mmol), 2,3,4,5,6-Pentafluorostyrene (58.2 mg, 0.3 mmol), 1,4-dioxane (1.0 mL)를 넣은 후 110 ℃에서 15 시간동안 교반하였다. TLC를 통하여 출발 물질이 완전히 사라짐을 확인한 후 1N 염산 (1 mL)을 사용하여 반응을 종결시켰다. 수용액 층을 EtOAc (3 mL × 3)로 씻어 주고, 추출한 유기층을 무수 MgSO4로 건조하여 여과하였다. 용매를 제거한 후 MeOH (0.5 mL)와 TMS-diazomethane (0.40 mL, 0.75 mmol, 2.0 M in hexane, 5.0 equiv)을 넣은 후 실온에서 30 분간 교반하였다. TLC를 통하여 출발 물질이 완전히 사라짐을 확인한 후 용매를 제거하였다. 관 크로마토그래피를 통하여 생성물인 (E)-2,3-dimethyl-6-(2-(perfluorophenyl)vinyl)phenyl dimethyl phosphate (46.2 mg, 73%)를 얻었다.Pd (OAc) 2 (3.36 mg, 0.015 mmol) and AgOAc (75.1 mg, 0.45 mmol) were added to a reaction v-vial (diameter 2 cm, height 4 cm) in a glove box and 2,3-dimethylphenyl methyl hydrogen 2,3,4,5,6-Pentafluorostyrene (58.2 mg, 0.3 mmol) and 1,4-dioxane (1.0 mL) were added to the solution, and the mixture was stirred at 110 ° C for 15 hours. After confirming that the starting material disappeared completely through TLC, the reaction was terminated using 1N hydrochloric acid (1 mL). The aqueous layer was washed with EtOAc (3 mL × 3), and the extracted organic layer was dried over anhydrous MgSO 4 and filtered. After removal of the solvent, MeOH (0.5 mL) and TMS-diazomethane (0.40 mL, 0.75 mmol, 2.0 M in hexane, 5.0 equiv) were added and stirred at room temperature for 30 min. After confirming that the starting material completely disappeared through TLC, the solvent was removed. (E) -2,3-dimethyl-6- (2- (perfluorophenyl) vinyl) phenyldimethyl phosphate (46.2 mg, 73%) was obtained through column chromatography.
1H NMR (400 MHz, CDCl3): δ 7.83 (d, J = 16.8 Hz, 1H), 7.43 (d, J = 8.0 Hz, 1H), 7.04 (d, J = 8.0 Hz, 1H), 6.91 (d, J = 16.8 Hz, 1H), 3.86 (d, J = 11.3 Hz, 6H), 2.31 (s, 3H), 2.29 (s, 3H) 1 H NMR (400 MHz, CDCl 3): δ 7.83 (d, J = 16.8 Hz, 1H), 7.43 (d, J = 8.0 Hz, 1H), 7.04 (d, J = 8.0 Hz, 1H), 6.91 ( d, J = 16.8 Hz, 1H ), 3.86 (d, J = 11.3 Hz, 6H), 2.31 (s, 3H), 2.29 (s, 3H)
[실시예 21] (E)-6-(4-클로로스타이릴)-2,3-다이메틸페닐 다이메틸 포스페이트 ((E)-6-(4-chlorostyryl)-2,3-dimethylphenyl dimethyl phosph -ate)의 제조[Example 21] (E) -6- (4-chlorostyryl) -2,3-dimethylphenyl dimethyl phosphate )
Glove box에서 반응용 v-바이알 (직경 : 2 cm, 높이 : 4 cm)에 Pd(OAc)2 (3.36 mg, 0.015 mmol ), AgOAc (75.1 mg, 0.45 mmol)를 넣고 2,3-dimethylphenyl methyl hydrogen phosphate (32.4 mg, 0.15 mmol), 4-chlorostyrene (41.6 mg, 0.3 mmol), 1,4-dioxane (1.0 mL)를 넣은 후 110 ℃에서 15 시간동안 교반하였다. TLC를 통하여 출발 물질이 완전히 사라짐을 확인한 후 1N 염산 (1 mL)을 사용하여 반응을 종결시켰다. 수용액 층을 EtOAc (3 mL × 3)로 씻어 주고, 추출한 유기층을 무수 MgSO4로 건조하여 여과하였다. 용매를 제거한 후 MeOH (0.5 mL)와 TMS-diazomethane (0.40 mL, 0.75 mmol, 2.0 M in hexane, 5.0 equiv)을 넣은 후 실온에서 30 분간 교반하였다. TLC를 통하여 출발 물질이 완전히 사라짐을 확인한 후 용매를 제거하였다. 관 크로마토그래피를 통하여 생성물인 (E)-6-(4-chlorostyryl)-2,3-dimethylphenyl dimethyl phosphate (39.6 mg, 72%)를 얻었다.Pd (OAc) 2 (3.36 mg, 0.015 mmol) and AgOAc (75.1 mg, 0.45 mmol) were added to a reaction v-vial (diameter 2 cm, height 4 cm) in a glove box and 2,3-dimethylphenyl methyl hydrogen 4-chlorostyrene (41.6 mg, 0.3 mmol) and 1,4-dioxane (1.0 mL) were added to the solution, and the mixture was stirred at 110 ° C for 15 hours. After confirming that the starting material disappeared completely through TLC, the reaction was terminated using 1N hydrochloric acid (1 mL). The aqueous layer was washed with EtOAc (3 mL × 3), and the extracted organic layer was dried over anhydrous MgSO 4 and filtered. After removal of the solvent, MeOH (0.5 mL) and TMS-diazomethane (0.40 mL, 0.75 mmol, 2.0 M in hexane, 5.0 equiv) were added and stirred at room temperature for 30 min. After confirming that the starting material completely disappeared through TLC, the solvent was removed. (E) -6- (4-chlorostyryl) -2,3-dimethylphenyl dimethylphosphate (39.6 mg, 72%) was obtained through column chromatography.
1H NMR (400 MHz, CDCl3): δ 7.53 - 7.43 (m, 3H), 7.41 (d, J = 8.0 Hz, 1H), 7.35 - 7.28 (m, 2H), 7.01 (d, J = 8.0 Hz, 1H), 6.96 (d, J = 16.3 Hz, 1H), 3.83 (d, J = 11.3 Hz, 6H), 2.29 (s, 3H), 2.28 (s, 3H) 1 H NMR (400 MHz, CDCl 3): δ 7.53 - 7.43 (m, 3H), 7.41 (d, J = 8.0 Hz, 1H), 7.35 - 7.28 (m, 2H), 7.01 (d, J = 8.0 Hz , 1H), 6.96 (d, J = 16.3 Hz, 1H), 3.83 (d, J = 11.3 Hz, 6H), 2.29 (s, 3H), 2.28 (s, 3H)
[실시예 22] (E)-2,3-다이메틸-6-(2-(나프탈렌-2-일)바이닐)페닐 다이메틸 포스페이트 ((E)-2,3-dimethyl-6-(2-(naphthalen-2-yl)vinyl)phenyl dimethyl phosphate)의 제조[Example 22] (E) -2,3-dimethyl-6- (2- (naphthalen-2-yl) (naphthalen-2-yl) vinyl) phenyl dimethyl phosphate
Glove box에서 반응용 v-바이알 (직경 : 2 cm, 높이 : 4 cm)에 Pd(OAc)2 (3.36 mg, 0.015 mmol ), AgOAc (75.1 mg, 0.45 mmol)를 넣고 2,3-dimethylphenyl methyl hydrogen phosphate (32.4 mg, 0.15 mmol), 1-vinylnaphthalene (46.3 mg, 0.3 mmol), 1,4-dioxane (1.0 mL)를 넣은 후 110 ℃에서 15 시간동안 교반하였다. TLC를 통하여 출발 물질이 완전히 사라짐을 확인한 후 1N 염산 (1 mL)을 사용하여 반응을 종결시켰다. 수용액 층을 EtOAc (3 mL × 3)로 씻어 주고, 추출한 유기층을 무수 MgSO4로 건조하여 여과하였다. 용매를 제거한 후 MeOH (0.5 mL)와 TMS-diazomethane (0.40 mL, 0.75 mmol, 2.0 M in hexane, 5.0 equiv)을 넣은 후 실온에서 30 분간 교반하였다. TLC를 통하여 출발 물질이 완전히 사라짐을 확인한 후 용매를 제거하였다. 관 크로마토그래피를 통하여 생성물인 (E)-2,3-dimethyl-6-(2-(naphthalen-2-yl)vinyl)phenyl dimethyl phosphate (36.7 mg, 64%)를 얻었다.Pd (OAc) 2 (3.36 mg, 0.015 mmol) and AgOAc (75.1 mg, 0.45 mmol) were added to a reaction v-vial (diameter 2 cm, height 4 cm) in a glove box and 2,3-dimethylphenyl methyl hydrogen phosphate (32.4 mg, 0.15 mmol), 1-vinylnaphthalene (46.3 mg, 0.3 mmol) and 1,4-dioxane (1.0 mL) were added thereto and stirred at 110 ° C for 15 hours. After confirming that the starting material disappeared completely through TLC, the reaction was terminated using 1N hydrochloric acid (1 mL). The aqueous layer was washed with EtOAc (3 mL × 3), and the extracted organic layer was dried over anhydrous MgSO 4 and filtered. After removal of the solvent, MeOH (0.5 mL) and TMS-diazomethane (0.40 mL, 0.75 mmol, 2.0 M in hexane, 5.0 equiv) were added and stirred at room temperature for 30 min. After confirming that the starting material completely disappeared through TLC, the solvent was removed. (E) -2,3-dimethyl-6- (2- (naphthalen-2-yl) vinyl) phenyldimethyl phosphate (36.7 mg, 64%) was obtained through column chromatography.
1H NMR (400 MHz, CDCl3): δ 7.88 - 7.74 (m, 5H), 7.63 (d, J = 16.3 Hz, 1H), 7.53 - 7.40 (m, 3H), 7.19 (d, J = 16.3 Hz, 1H), 7.04 (d, J = 8.0 Hz, 1H), 3.84 (d, J = 11.3 Hz, 6H), 2.31 (s, 6H) 1 H NMR (400 MHz, CDCl 3): δ 7.88 - 7.74 (m, 5H), 7.63 (d, J = 16.3 Hz, 1H), 7.53 - 7.40 (m, 3H), 7.19 (d, J = 16.3 Hz , 1H), 7.04 (d, J = 8.0 Hz, 1H), 3.84 (d, J = 11.3 Hz, 6H), 2.31 (s, 6H)
[실시예 23] (E)-2,3-다이메틸-6-(3-옥소-3-페닐프로프-1-엔-1-일)페닐 다이메틸 포스페이트 ((E)-2,3-dimethyl-6-(3-oxo-3-phenylprop-1-en-1-yl)phenyl dimethyl phosphate)의 제조
[Example 23] (E) -2,3-Dimethyl-6- (3-oxo-3-phenylprop-1-en-1-yl) phenyldimethylphosphate ((E) dimethyl-6- (3-oxo-3-phenylprop-1-en-1-yl) phenyl dimethyl phosphate
Glove box에서 반응용 v-바이알 (직경 : 2 cm, 높이 : 4 cm)에 Pd(OAc)2 (3.36 mg, 0.015mmol), AgOAc (75.1 mg, 0.45 mmol)를 넣고 2,3-dimethylphenyl methyl hydrogen phosphate (32.4 mg, 0.15 mmol), 1-phenylprop-2-en-1-one (39.6 mg, 0.3 mmol), 1,4-dioxane (1.0 mL)를 넣은 후 110 ℃에서 15 시간동안 교반하였다. TLC를 통하여 출발 물질이 완전히 사라짐을 확인한 후 1N 염산 (1 mL)을 사용하여 반응을 종결시켰다. 수용액 층을 EtOAc (3 mL × 3)로 씻어 주고, 추출한 유기층을 무수 MgSO4로 건조하여 여과하였다. 용매를 제거한 후 MeOH (0.5 mL)와 TMS-diazomethane (0.40 mL, 0.75 mmol, 2.0 M in hexane, 5.0 equiv)을 넣은 후 실온에서 30 분간 교반하였다. TLC를 통하여 출발 물질이 완전히 사라짐을 확인한 후 용매를 제거하였다. 관 크로마토그래피를 통하여 생성물인 (E)-2,3-dimethyl-6-(3-oxo-3-phenylprop-1-en-1-yl)phenyl dimethyl phosphate (36.2 mg, 67%)를 얻었다.Pd (OAc) 2 (3.36 mg, 0.015 mmol) and AgOAc (75.1 mg, 0.45 mmol) were added to a reaction v-vial (diameter 2 cm, height 4 cm) 2-en-1-one (39.6 mg, 0.3 mmol) and 1,4-dioxane (1.0 mL) were added and the mixture was stirred at 110 ° C for 15 hours. After confirming that the starting material disappeared completely through TLC, the reaction was terminated using 1N hydrochloric acid (1 mL). The aqueous layer was washed with EtOAc (3 mL × 3), and the extracted organic layer was dried over anhydrous MgSO 4 and filtered. After removal of the solvent, MeOH (0.5 mL) and TMS-diazomethane (0.40 mL, 0.75 mmol, 2.0 M in hexane, 5.0 equiv) were added and stirred at room temperature for 30 min. After confirming that the starting material completely disappeared through TLC, the solvent was removed. The product, (E) -2,3-dimethyl-6- (3-oxo-3-phenylprop-1-en-1-yl) phenyldimethylphosphate (36.2 mg, 67%) was obtained by column chromatography.
1H NMR (400 MHz, CDCl3): δ 8.14 (d, J = 15.8 Hz, 1H), 8.07 - 7.94 (m, 2H), 7.63 - 7.54 (m, 1H), 7.55 - 7.42 (m, 4H), 7.06 (d, J = 7.9 Hz, 1H), 3.86 (d, J = 11.4 Hz, 6H), 2.33 (s, 3H), 2.31 (s, 3H)
1 H NMR (400 MHz, CDCl 3): δ 8.14 (d, J = 15.8 Hz, 1H), 8.07 - 7.94 (m, 2H), 7.63 - 7.54 (m, 1H), 7.55 - 7.42 (m, 4H) , 7.06 (d, J = 7.9 Hz, 1H), 3.86 (d, J = 11.4 Hz, 6H), 2.33
Claims (9)
[화학식 1]
[상기 화학식 1에서 R1은 (C1-C30)알킬, (C6-C30)아릴, (C6-C30)아르(C1-C20)알킬, -C(=O)Ra,-C(=O)ORa, -S(=O)2Ra 및 -P(=O)(Ra)2 로부터 선택되어지고, 상기 Ra는 (C1-C30)알킬, (C1-C20)알콕시, (C6-C30)아릴 및 (C6-C30)아르(C1-C20)알킬로부터 선택되어지고, 상기 아릴은 할로겐 또는 (C1-C10)알킬로 더 치환될 수 있으며, R2 내지 R5 는 서로 독립적으로 할로겐, (C1-C30)알킬, (C1-C20)알콕시 및 (C3-C20)사이클로알킬로부터 선택되어지고, R4 와 R5는 인접한 (C2-C10)알케닐렌 또는 (C2-C10)알키닐렌으로 연결되어 융합고리를 형성 할 수 있으며, R6 및 R7은 서로 독립적으로 수소, 하이드록시, (C1-C10)알킬 및 (C1-C10)알콕시로부터 선택될 수 있다.]A 2-vinylphenylphosphate derivative compound represented by the following formula (1).
[Chemical Formula 1]
[R 1 is a (C1-C30) alkyl, (C6-C30) aryl, (C6-C30) aralkyl (C1-C20) alkyl, -C (= O) R a , -C (= O) in the general formula (1) OR a , -S (= O) 2 R a and -P (= O) (R a ) 2 Selected, Wherein R a is selected from (C 1 -C 30) alkyl, (C 1 -C 20) alkoxy, (C 6 -C 30) aryl and (C 6 -C 30) C10) alkyl, < / RTI > R 2 To R 5 are independently selected from halogen, (C 1 -C 30) alkyl, (C 1 -C 20) alkoxy and (C 3 -C 20) cycloalkyl, R 4 and R 5 are selected from the group consisting of adjacent (C 2 -C 10) alkenylene or (C2-C10) connected to alkynylene may form a fused ring, R 6 and R 7 independently can be selected from hydrogen, hydroxy, (C1-C10) alkyl and (C1-C10) alkoxy each other .]
상기 화학식 1에서 R1은 에톡시카보닐, 벤질옥시카보닐, 1-나프틸, 페닐, 파라클로로페닐, 헥사클로로페닐, 벤조일, 다이에틸포스포릴 및 페닐썰포닐로부터 선택되며;
R3 내지 R5 는 서로 독립적으로 수소, 메틸, t-부틸, 메톡시, 페닐, 벤질, 아다만틸, 플로로 및 클로로로부터 선택되며;
상기 R4 와 R5는 인접한 에틸렌 또는 아세틸렌으로 연결되어
Wherein R 1 is selected from ethoxycarbonyl, benzyloxycarbonyl, 1-naphthyl, phenyl, para-chlorophenyl, hexachlorophenyl, benzoyl, diethylphosphoryl and phenylsulfonyl;
R 3 to R 5 are independently from each other selected from hydrogen, methyl, t-butyl, methoxy, phenyl, benzyl, adamantyl, fluoro and chloro;
Wherein R < 4 > and R < 5 > are connected to adjacent ethylene or acetylene
상기 2-바이닐페닐 포스페이트 화합물은 하기 화합물로부터 선택되는 것을 특징으로 하는 2-바이닐페닐 포스페이트 화합물.
The 2-vinylphenylphosphate compound is selected from the following compounds.
[화학식 2]
[화학식 3]
[화학식 1]
[상기 화학식 1 및 화학식 3에서 R1은 (C1-C30)알킬, (C6-C30)아릴, (C6-C30)아르(C1-C20)알킬, -C(=O)Ra,-C(=O)ORa, -S(=O)2Ra 및 -P(=O)(Ra)2 로부터 선택되어지고, 상기 Ra는 (C1-C30)알킬, (C1-C20)알콕시, (C6-C30)아릴 및 (C6-C30)아르(C1-C20)알킬로부터 선택되어지고, 상기 아릴은 할로겐 또는 (C1-C10)알킬로 더 치환될 수 있으며, 상기 화학식 1 및 화학식 2에서 R2 내지 R5 는 서로 독립적으로 할로겐, (C1-C30)알킬, (C1-C20)알콕시 및 (C1-C20)사이클로알킬로부터 선택되어지고, R4 와 R5는 인접한 (C2-C10)알케닐렌 또는 (C2-C10)알키닐렌으로 연결되어 융합고리를 형성 할 수 있으며, 상기 화학식 1 및 화학식 2에서 R6 및 R7은 서로 독립적으로 수소, 하이드록시, (C1-C10)알킬 및 (C1-C10)알콕시로부터 선택될 수 있다.] (2) in the presence of a palladium catalyst and an additive by reacting a phosphate compound represented by the following formula (2) with a vinyl compound represented by the following formula (3).
(2)
(3)
[Chemical Formula 1]
[In Formula 1 and Formula 3 R 1 is (C1-C30) alkyl, (C6-C30) aryl, (C6-C30) aralkyl (C1-C20) alkyl, -C (= O) R a , -C ( = O) OR a , -S (= O) 2 R a and -P (= O) (R a ) 2 Selected, Wherein R a is selected from (C 1 -C 30) alkyl, (C 1 -C 20) alkoxy, (C 6 -C 30) aryl and (C 6 -C 30) C10) alkyl, < / RTI > In the above formulas (1) and (2), R 2 To R 5 are independently selected from halogen, (C 1 -C 30) alkyl, (C 1 -C 20) alkoxy and (C 1 -C 20) cycloalkyl, R 4 and R 5 are adjacent (C 2 -C 10) alkenylene or (C2-C10) may be connected to the alkynylene to form a fused ring, in the formula 1) and (2 R 6 and R 7 are independently hydrogen, hydroxy each other, (C1-C10) alkyl and (C1-C10 ) Alkoxy. ≪ / RTI >
팔라듐(Pd)촉매는 Pd(OAc)2 [OAc : acetate], Pd(TFA)2 [TFA : trifluoroacetic acid], PdCl2, PdBr2, PdCl2(MeCN)2, [(C6H5)3P]2PdCl2 , Pd(dppf)Cl2 [dppf : 1,1'-Bis(diphenylphosphino)ferrocene 및 [PdCl(C3H5)]2 에서 선택되는 하나 이상인 것을 특징으로 하는 2-바이닐페닐 포스페이트 유도체 화합물의 제조방법.5. The method of claim 4,
Palladium (Pd) catalyst is Pd (OAc) 2 [OAc: acetate], Pd (TFA) 2 [TFA: trifluoroacetic acid], PdCl 2, PdBr 2, PdCl 2 (MeCN) 2, [(C 6 H 5) 3 P] 2 PdCl 2, Pd ( dppf) Cl 2 [dppf: 1,1'-Bis (diphenylphosphino) ferrocene and [PdCl (C 3 H 5) ] 2- vinyl-phenyl phosphate, characterized in that at least one selected from 2 ≪ / RTI >
상기 팔라듐 촉매의 양은 상기 화학식 2로 표시되는 포스페이트 유도체에 대해 0.01 내지 0.5몰을 사용하는 것을 특징으로 하는 2-바이닐페닐 포스페이트 유도체 화합물의 제조방법.6. The method of claim 5,
Wherein the amount of the palladium catalyst is 0.01 to 0.5 mol based on the amount of the phosphate derivative represented by the formula (2).
상기 첨가제는 CuCl, Cu2O, CuO, Cu(OAc)2, Cu(OTf)2 [OTf : trifluoromethanesulfonate], Ag2O, AgO, AgOAc, Ag2CO3, Na2K2O8, K2S2O8, NaOAc, BQ [BQ : benzoquinone], NIS(N-iodosuccinimide), NCS(N-chlorosuccinimide, FeCl3, Mn(OAc)3 2H2O, V2O5, PhI(OAc)2, PhI(TFA)2, IOAc, Oxone 및 O2에서 선택되는 하나 이상인 것을 특징으로 하는 2-바이닐페닐 포스페이트 유도체 화합물의 제조방법.5. The method of claim 4,
The additive CuCl, Cu 2 O, CuO, Cu (OAc) 2, Cu (OTf) 2 [OTf: trifluoromethanesulfonate], Ag 2 O, AgO, AgOAc, Ag 2 CO 3, Na 2 K 2 O 8, K 2 S 2 O 8, NaOAc, BQ [BQ: benzoquinone], NIS (N -iodosuccinimide), NCS (N -chlorosuccinimide, FeCl 3, Mn (OAc) 3 2H 2 O, V 2 O 5, PhI (OAc) 2, PhI (TFA) 2, IOAc, Oxone, and O 2. 2. A process for producing a 2- vinylphenylphosphate derivative compound according to claim 1,
상기 첨가제의 양은 상기 화학식 2로 표시되는 포스페이트 유도체에 대해 1 내지 5몰을 사용하는 2-바이닐페닐 포스페이트 유도체 화합물의 제조방법.The method of claim 7, wherein
Wherein the amount of the additive is 1 to 5 moles relative to the phosphate derivative represented by the formula (2).
상기 화학식3의 바이닐 화합물은 상기 화학식 2의 화합물에 대해 1 내지 5 몰로 사용하는것을 특징으로 하는 상기 화학식 1의2-바이닐페닐 포스페이트 유도체 화합물의 제조방법.
5. The method of claim 4,
Wherein the vinyl compound of formula (3) is used in an amount of 1 to 5 moles relative to the compound of formula (2).
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| CN109524715A (en) * | 2018-11-22 | 2019-03-26 | 桑顿新能源科技有限公司 | A kind of lithium-ion battery electrolytes additive and electrolyte and lithium ion battery |
| CN117059804A (en) * | 2023-10-13 | 2023-11-14 | 瑞浦兰钧能源股份有限公司 | Chemical pre-lithium agent, lithium ion battery and preparation method of lithium ion battery |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| KR20160109403A (en) * | 2015-03-11 | 2016-09-21 | 강원대학교산학협력단 | Novel vinyl phosphacoumarin derivatives and its preparation method |
| CN109524715A (en) * | 2018-11-22 | 2019-03-26 | 桑顿新能源科技有限公司 | A kind of lithium-ion battery electrolytes additive and electrolyte and lithium ion battery |
| CN109524715B (en) * | 2018-11-22 | 2021-09-17 | 桑顿新能源科技(长沙)有限公司 | Additive for lithium ion battery electrolyte, electrolyte and lithium ion battery |
| CN117059804A (en) * | 2023-10-13 | 2023-11-14 | 瑞浦兰钧能源股份有限公司 | Chemical pre-lithium agent, lithium ion battery and preparation method of lithium ion battery |
| CN117059804B (en) * | 2023-10-13 | 2024-03-19 | 瑞浦兰钧能源股份有限公司 | Chemical pre-lithium agent, lithium ion battery and preparation method of lithium ion battery |
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