JP6578116B2 - 一置換(フルオロアルキル)エチレン類及びその製造方法 - Google Patents
一置換(フルオロアルキル)エチレン類及びその製造方法 Download PDFInfo
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- JP6578116B2 JP6578116B2 JP2015062367A JP2015062367A JP6578116B2 JP 6578116 B2 JP6578116 B2 JP 6578116B2 JP 2015062367 A JP2015062367 A JP 2015062367A JP 2015062367 A JP2015062367 A JP 2015062367A JP 6578116 B2 JP6578116 B2 JP 6578116B2
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- 125000003709 fluoroalkyl group Chemical group 0.000 title claims description 33
- 125000000816 ethylene group Chemical class [H]C([H])([*:1])C([H])([H])[*:2] 0.000 title claims description 16
- 238000000034 method Methods 0.000 title description 7
- -1 1,3,2-dioxaborolan-2-yl group Chemical group 0.000 claims description 348
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 86
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 60
- 125000004432 carbon atom Chemical group C* 0.000 claims description 49
- 229910052763 palladium Inorganic materials 0.000 claims description 43
- 238000004519 manufacturing process Methods 0.000 claims description 34
- WDUDHEOUGWAKFD-UHFFFAOYSA-N ditert-butyl(cyclopenta-2,4-dien-1-yl)phosphane;iron(2+) Chemical compound [Fe+2].CC(C)(C)P(C(C)(C)C)C1=CC=C[CH-]1.CC(C)(C)P(C(C)(C)C)C1=CC=C[CH-]1 WDUDHEOUGWAKFD-UHFFFAOYSA-N 0.000 claims description 23
- 125000000217 alkyl group Chemical group 0.000 claims description 22
- 125000003963 dichloro group Chemical group Cl* 0.000 claims description 22
- 239000003054 catalyst Substances 0.000 claims description 21
- 150000001875 compounds Chemical class 0.000 claims description 21
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 21
- 125000003545 alkoxy group Chemical group 0.000 claims description 17
- 229910052783 alkali metal Inorganic materials 0.000 claims description 16
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 14
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- 150000002941 palladium compounds Chemical class 0.000 claims description 10
- 239000005977 Ethylene Substances 0.000 claims description 8
- 125000002252 acyl group Chemical group 0.000 claims description 8
- BWHDROKFUHTORW-UHFFFAOYSA-N tritert-butylphosphane Chemical compound CC(C)(C)P(C(C)(C)C)C(C)(C)C BWHDROKFUHTORW-UHFFFAOYSA-N 0.000 claims description 8
- 150000001639 boron compounds Chemical class 0.000 claims description 7
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
- 229910052731 fluorine Inorganic materials 0.000 claims description 6
- 125000001153 fluoro group Chemical group F* 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 229910000288 alkali metal carbonate Inorganic materials 0.000 claims description 4
- 150000008041 alkali metal carbonates Chemical group 0.000 claims description 4
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 4
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 125000004469 siloxy group Chemical group [SiH3]O* 0.000 claims description 4
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 claims description 4
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical group C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 3
- 229910001515 alkali metal fluoride Inorganic materials 0.000 claims description 3
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims description 3
- 229910000318 alkali metal phosphate Inorganic materials 0.000 claims description 3
- 125000003342 alkenyl group Chemical group 0.000 claims description 3
- 125000004414 alkyl thio group Chemical group 0.000 claims description 3
- 125000003118 aryl group Chemical group 0.000 claims description 3
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 3
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 3
- 125000001188 haloalkyl group Chemical group 0.000 claims description 3
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 3
- 229910052700 potassium Inorganic materials 0.000 claims description 3
- 239000011591 potassium Substances 0.000 claims description 3
- 229910052708 sodium Inorganic materials 0.000 claims description 3
- 239000011734 sodium Substances 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
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 2
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
- 125000004244 benzofuran-2-yl group Chemical group [H]C1=C(*)OC2=C([H])C([H])=C([H])C([H])=C12 0.000 claims description 2
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 2
- 125000001626 borono group Chemical group [H]OB([*])O[H] 0.000 claims description 2
- TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical class [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 claims description 2
- 150000001721 carbon Chemical group 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 125000004548 quinolin-3-yl group Chemical group N1=CC(=CC2=CC=CC=C12)* 0.000 claims description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 198
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 165
- 238000006243 chemical reaction Methods 0.000 description 121
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 99
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 96
- 239000000203 mixture Substances 0.000 description 72
- 238000005160 1H NMR spectroscopy Methods 0.000 description 54
- 238000010898 silica gel chromatography Methods 0.000 description 54
- 239000012300 argon atmosphere Substances 0.000 description 51
- 239000012153 distilled water Substances 0.000 description 48
- LDTMPQQAWUMPKS-OWOJBTEDSA-N (e)-1-chloro-3,3,3-trifluoroprop-1-ene Chemical compound FC(F)(F)\C=C\Cl LDTMPQQAWUMPKS-OWOJBTEDSA-N 0.000 description 47
- XYQRXRFVKUPBQN-UHFFFAOYSA-L Sodium carbonate decahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.[Na+].[Na+].[O-]C([O-])=O XYQRXRFVKUPBQN-UHFFFAOYSA-L 0.000 description 46
- 229940018038 sodium carbonate decahydrate Drugs 0.000 description 46
- 238000005481 NMR spectroscopy Methods 0.000 description 45
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 42
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 38
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
- 239000007787 solid Substances 0.000 description 31
- 239000007788 liquid Substances 0.000 description 24
- 239000000243 solution Substances 0.000 description 23
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
- 238000004817 gas chromatography Methods 0.000 description 15
- 235000011121 sodium hydroxide Nutrition 0.000 description 14
- 230000015572 biosynthetic process Effects 0.000 description 13
- JMQRNHTTZWNLMH-UHFFFAOYSA-M 1,3-bis(2,4,6-trimethylphenyl)imidazole;chlorocopper Chemical compound CC1=CC(C)=CC(C)=C1N1C(=[Cu]Cl)N(C=2C(=CC(C)=CC=2C)C)C=C1 JMQRNHTTZWNLMH-UHFFFAOYSA-M 0.000 description 11
- LUDPTKMULHKDEW-BQYQJAHWSA-N 2-[(e)-3,3,3-trifluoroprop-1-enyl]naphthalene Chemical compound C1=CC=CC2=CC(/C=C/C(F)(F)F)=CC=C21 LUDPTKMULHKDEW-BQYQJAHWSA-N 0.000 description 11
- SKTCDJAMAYNROS-UHFFFAOYSA-N methoxycyclopentane Chemical compound COC1CCCC1 SKTCDJAMAYNROS-UHFFFAOYSA-N 0.000 description 11
- HTZWATKNQYOOIT-UHFFFAOYSA-N 2-(1,3,2-dioxaborolan-2-yl)-1,3,2-dioxaborolane Chemical compound O1CCOB1B1OCCO1 HTZWATKNQYOOIT-UHFFFAOYSA-N 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- KPTRDYONBVUWPD-UHFFFAOYSA-N naphthalen-2-ylboronic acid Chemical compound C1=CC=CC2=CC(B(O)O)=CC=C21 KPTRDYONBVUWPD-UHFFFAOYSA-N 0.000 description 9
- XJHCXCQVJFPJIK-UHFFFAOYSA-M caesium fluoride Chemical compound [F-].[Cs+] XJHCXCQVJFPJIK-UHFFFAOYSA-M 0.000 description 8
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 230000000052 comparative effect Effects 0.000 description 7
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 6
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 6
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 6
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
- 239000002994 raw material Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- 0 CCCCC(*1OC(C)(C)C(C)(C)O1)=Cc(cc1)ccc1C(C)=O Chemical compound CCCCC(*1OC(C)(C)C(C)(C)O1)=Cc(cc1)ccc1C(C)=O 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 4
- 229910000024 caesium carbonate Inorganic materials 0.000 description 4
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 4
- 229940095102 methyl benzoate Drugs 0.000 description 4
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 235000011181 potassium carbonates Nutrition 0.000 description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- QIVUCLWGARAQIO-OLIXTKCUSA-N (3s)-n-[(3s,5s,6r)-6-methyl-2-oxo-1-(2,2,2-trifluoroethyl)-5-(2,3,6-trifluorophenyl)piperidin-3-yl]-2-oxospiro[1h-pyrrolo[2,3-b]pyridine-3,6'-5,7-dihydrocyclopenta[b]pyridine]-3'-carboxamide Chemical compound C1([C@H]2[C@H](N(C(=O)[C@@H](NC(=O)C=3C=C4C[C@]5(CC4=NC=3)C3=CC=CN=C3NC5=O)C2)CC(F)(F)F)C)=C(F)C=CC(F)=C1F QIVUCLWGARAQIO-OLIXTKCUSA-N 0.000 description 3
- 125000006002 1,1-difluoroethyl group Chemical group 0.000 description 3
- 125000005919 1,2,2-trimethylpropyl group Chemical group 0.000 description 3
- 125000005918 1,2-dimethylbutyl group Chemical group 0.000 description 3
- 125000006218 1-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 3
- KUGORIVFZREOBQ-ZHACJKMWSA-N 1-phenylmethoxy-4-[(e)-3,3,3-trifluoroprop-1-enyl]benzene Chemical compound C1=CC(/C=C/C(F)(F)F)=CC=C1OCC1=CC=CC=C1 KUGORIVFZREOBQ-ZHACJKMWSA-N 0.000 description 3
- 125000004778 2,2-difluoroethyl group Chemical group [H]C([H])(*)C([H])(F)F 0.000 description 3
- VTBGENTZANWBTA-GORDUTHDSA-N 2-[(e)-prop-1-enyl]naphthalene Chemical compound C1=CC=CC2=CC(/C=C/C)=CC=C21 VTBGENTZANWBTA-GORDUTHDSA-N 0.000 description 3
- 125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 3
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 3
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 3
- 125000005916 2-methylpentyl group Chemical group 0.000 description 3
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 3
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 3
- 125000003542 3-methylbutan-2-yl group Chemical group [H]C([H])([H])C([H])(*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 125000005917 3-methylpentyl group Chemical group 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- WXNOJTUTEXAZLD-UHFFFAOYSA-L benzonitrile;dichloropalladium Chemical compound Cl[Pd]Cl.N#CC1=CC=CC=C1.N#CC1=CC=CC=C1 WXNOJTUTEXAZLD-UHFFFAOYSA-L 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 3
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 3
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- RDONXGFGWSSFMY-UHFFFAOYSA-N n-[4-(2,4-difluorophenoxy)-3-(6-methyl-7-oxo-1h-pyrrolo[2,3-c]pyridin-4-yl)phenyl]ethanesulfonamide Chemical compound C=1N(C)C(=O)C=2NC=CC=2C=1C1=CC(NS(=O)(=O)CC)=CC=C1OC1=CC=C(F)C=C1F RDONXGFGWSSFMY-UHFFFAOYSA-N 0.000 description 3
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- JKDRQYIYVJVOPF-FDGPNNRMSA-L palladium(ii) acetylacetonate Chemical compound [Pd+2].C\C([O-])=C\C(C)=O.C\C([O-])=C\C(C)=O JKDRQYIYVJVOPF-FDGPNNRMSA-L 0.000 description 3
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 3
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 3
- 239000011698 potassium fluoride Substances 0.000 description 3
- 235000003270 potassium fluoride Nutrition 0.000 description 3
- 229910000160 potassium phosphate Inorganic materials 0.000 description 3
- 235000011009 potassium phosphates Nutrition 0.000 description 3
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 229940001593 sodium carbonate Drugs 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- BIIBYWQGRFWQKM-JVVROLKMSA-N (2S)-N-[4-(cyclopropylamino)-3,4-dioxo-1-[(3S)-2-oxopyrrolidin-3-yl]butan-2-yl]-2-[[(E)-3-(2,4-dichlorophenyl)prop-2-enoyl]amino]-4,4-dimethylpentanamide Chemical compound CC(C)(C)C[C@@H](C(NC(C[C@H](CCN1)C1=O)C(C(NC1CC1)=O)=O)=O)NC(/C=C/C(C=CC(Cl)=C1)=C1Cl)=O BIIBYWQGRFWQKM-JVVROLKMSA-N 0.000 description 2
- DNBCBAXDWNDRNO-FOSCPWQOSA-N (3aS,6aR)-N-(3-methoxy-1,2,4-thiadiazol-5-yl)-5-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carboxamide Chemical compound COC1=NSC(NC(=O)N2C[C@H]3CC(C[C@H]3C2)N(C)C=2C=3C=CNC=3N=CN=2)=N1 DNBCBAXDWNDRNO-FOSCPWQOSA-N 0.000 description 2
- DMJHEIDWSIAXCS-UHFFFAOYSA-N (4-phenylmethoxyphenyl)boronic acid Chemical compound C1=CC(B(O)O)=CC=C1OCC1=CC=CC=C1 DMJHEIDWSIAXCS-UHFFFAOYSA-N 0.000 description 2
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- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 150000008366 benzophenones Chemical group 0.000 description 1
- JRXXLCKWQFKACW-UHFFFAOYSA-N biphenylacetylene Chemical compound C1=CC=CC=C1C#CC1=CC=CC=C1 JRXXLCKWQFKACW-UHFFFAOYSA-N 0.000 description 1
- 125000004744 butyloxycarbonyl group Chemical group 0.000 description 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- ZMCUDHNSHCRDBT-UHFFFAOYSA-M caesium bicarbonate Chemical compound [Cs+].OC([O-])=O ZMCUDHNSHCRDBT-UHFFFAOYSA-M 0.000 description 1
- HUCVOHYBFXVBRW-UHFFFAOYSA-M caesium hydroxide Inorganic materials [OH-].[Cs+] HUCVOHYBFXVBRW-UHFFFAOYSA-M 0.000 description 1
- AMJQWGIYCROUQF-UHFFFAOYSA-N calcium;methanolate Chemical compound [Ca+2].[O-]C.[O-]C AMJQWGIYCROUQF-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 159000000006 cesium salts Chemical class 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- IHPFQAOOSAGSPN-UHFFFAOYSA-N dodec-6-yne Chemical compound CCCCCC#CCCCCC IHPFQAOOSAGSPN-UHFFFAOYSA-N 0.000 description 1
- XUZICJHIIJCKQQ-ZDUSSCGKSA-N eclitasertib Chemical compound C(C1=CC=CC=C1)C=1NC(=NN=1)C(=O)N[C@@H]1C(N(C2=C(OC1)C=CC=N2)C)=O XUZICJHIIJCKQQ-ZDUSSCGKSA-N 0.000 description 1
- 239000004210 ether based solvent Substances 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- 125000006627 ethoxycarbonylamino group Chemical group 0.000 description 1
- 125000006125 ethylsulfonyl group Chemical group 0.000 description 1
- 125000004705 ethylthio group Chemical group C(C)S* 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 125000005446 heptyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 125000003707 hexyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
- 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 description 1
- 229910052808 lithium carbonate Inorganic materials 0.000 description 1
- 229940008015 lithium carbonate Drugs 0.000 description 1
- 125000005394 methallyl group Chemical group 0.000 description 1
- CKJNUZNMWOVDFN-UHFFFAOYSA-N methanone Chemical compound O=[CH-] CKJNUZNMWOVDFN-UHFFFAOYSA-N 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000006626 methoxycarbonylamino group Chemical group 0.000 description 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
- YBXBWBBVLXZQBJ-UHFFFAOYSA-N n-[2-(5-hydroxy-2-methyl-1h-indol-3-yl)ethyl]-2-methoxyacetamide Chemical compound C1=C(O)C=C2C(CCNC(=O)COC)=C(C)NC2=C1 YBXBWBBVLXZQBJ-UHFFFAOYSA-N 0.000 description 1
- VZUGBLTVBZJZOE-KRWDZBQOSA-N n-[3-[(4s)-2-amino-1,4-dimethyl-6-oxo-5h-pyrimidin-4-yl]phenyl]-5-chloropyrimidine-2-carboxamide Chemical compound N1=C(N)N(C)C(=O)C[C@@]1(C)C1=CC=CC(NC(=O)C=2N=CC(Cl)=CN=2)=C1 VZUGBLTVBZJZOE-KRWDZBQOSA-N 0.000 description 1
- HUMMCEUVDBVXTQ-UHFFFAOYSA-N naphthalen-1-ylboronic acid Chemical compound C1=CC=C2C(B(O)O)=CC=CC2=C1 HUMMCEUVDBVXTQ-UHFFFAOYSA-N 0.000 description 1
- 125000005447 octyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- HQIXAWUUYCUDJA-UHFFFAOYSA-N oxolane;prop-1-ene Chemical compound CC=C.C1CCOC1 HQIXAWUUYCUDJA-UHFFFAOYSA-N 0.000 description 1
- 150000002940 palladium Chemical class 0.000 description 1
- PENAXHPKEVTBLF-UHFFFAOYSA-L palladium(2+);prop-1-ene;dichloride Chemical class [Pd+]Cl.[Pd+]Cl.[CH2-]C=C.[CH2-]C=C PENAXHPKEVTBLF-UHFFFAOYSA-L 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- INIOZDBICVTGEO-UHFFFAOYSA-L palladium(ii) bromide Chemical compound Br[Pd]Br INIOZDBICVTGEO-UHFFFAOYSA-L 0.000 description 1
- 125000004115 pentoxy group Chemical group [*]OC([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- FVZVCSNXTFCBQU-UHFFFAOYSA-N phosphanyl Chemical group [PH2] FVZVCSNXTFCBQU-UHFFFAOYSA-N 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000004262 preparative liquid chromatography Methods 0.000 description 1
- 238000012746 preparative thin layer chromatography Methods 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
- YGDICLRMNDWZAK-UHFFFAOYSA-N quinolin-3-ylboronic acid Chemical compound C1=CC=CC2=CC(B(O)O)=CN=C21 YGDICLRMNDWZAK-UHFFFAOYSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- WPFGFHJALYCVMO-UHFFFAOYSA-L rubidium carbonate Chemical compound [Rb+].[Rb+].[O-]C([O-])=O WPFGFHJALYCVMO-UHFFFAOYSA-L 0.000 description 1
- 229910000026 rubidium carbonate Inorganic materials 0.000 description 1
- KBAHJOGZLVQNBH-UHFFFAOYSA-K rubidium(1+);phosphate Chemical compound [Rb+].[Rb+].[Rb+].[O-]P([O-])([O-])=O KBAHJOGZLVQNBH-UHFFFAOYSA-K 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 125000005930 sec-butyloxycarbonyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
- OEBIHOVSAMBXIB-SJKOYZFVSA-N selitrectinib Chemical compound C[C@@H]1CCC2=NC=C(F)C=C2[C@H]2CCCN2C2=NC3=C(C=NN3C=C2)C(=O)N1 OEBIHOVSAMBXIB-SJKOYZFVSA-N 0.000 description 1
- 239000011775 sodium fluoride Substances 0.000 description 1
- 235000013024 sodium fluoride Nutrition 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 229940083608 sodium hydroxide Drugs 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 238000000859 sublimation Methods 0.000 description 1
- 230000008022 sublimation Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- FVDLAPLZIFUTTF-ZHACJKMWSA-N tert-butyl-dimethyl-[4-[(E)-3,3,3-trifluoroprop-1-enyl]phenoxy]silane Chemical compound O([Si](C)(C)C(C)(C)C)C1=CC=C(C=C1)\C=C\C(F)(F)F FVDLAPLZIFUTTF-ZHACJKMWSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 125000002306 tributylsilyl group Chemical group C(CCC)[Si](CCCC)(CCCC)* 0.000 description 1
- 125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 description 1
- POTUCPCPDUCNAM-CMDGGOBGSA-N trimethyl-[4-[(E)-3,3,3-trifluoroprop-1-enyl]phenyl]silane Chemical compound C[Si](C1=CC=C(C=C1)\C=C\C(F)(F)F)(C)C POTUCPCPDUCNAM-CMDGGOBGSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- BWHDROKFUHTORW-UHFFFAOYSA-O tritert-butylphosphanium Chemical compound CC(C)(C)[PH+](C(C)(C)C)C(C)(C)C BWHDROKFUHTORW-UHFFFAOYSA-O 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
Description
(i)一般式(1)
(ii)水が有機ホウ素化合物(2)に対して10〜100モル当量である(i)に記載の製造方法;
(iii)アルキルホスフィン配位パラジウム触媒が、パラジウム化合物とアルキルホスフィン化合物から調製した触媒である(i)または(ii)に記載の製造方法;
(iv)アルキルホスフィン化合物が、トリ−tert−ブチルホスフィン、トリ−tert−ブチルホスホニウムテトラフルオロボラートまたは1,1’−ビス(ジ−tert−ブチルホスフィノ)フェロセンである(iii)に記載の製造方法;
(v)アルキルホスフィン配位パラジウム触媒が、ジクロロ[1,1’−ビス(ジ−tert−ブチルホスフィノ)フェロセン]パラジウムである(i)または(ii)に記載の製造方法;
(vi)アルカリ金属塩が炭酸アルカリ金属塩、炭酸水素アルカリ金属塩、フッ化アルカリ金属塩、水酸化アルカリ金属塩またはリン酸アルカリ金属塩である(i)から(v)のいずれかに記載の製造方法;
(vii)アルカリ金属塩がナトリウム、カリウムまたはセシウム塩である(i)から(vi)のいずれかに記載の製造方法;
(viii)Rfがトリフルオロメチル基である(i)から(vii)のいずれかに記載の製造方法;
(ix)
一般式(5a)
1H−NMR(CDCl3,400MHz)δ7.44−7.34(m,7H),7.08(qd,J=2.2Hz,16.1Hz,1H),7.00−6.96(m,2H),6.06(qd,J=6.6Hz,16.1Hz,1H),5.09(s,2H);19F−NMR(CDCl3,376MHz)δ−62.9(s,3F).
トリス(ジベンジリデンアセトン)ジパラジウム及びトリ−tert−ブチルホスホニウムテトラフルオロボラートに替えてジクロロ[1,1’−ビス(ジフェニルホスフィノ)フェロセン]パラジウム3.7mg(0.005mmol)を用いた以外は全て実施例−1と同じ操作を行い、(E)−1−(ベンジルオキシ)−4−(3,3,3−トリフルオロ−1−プロペン−1−イル)ベンゼン58mg(白色固体、収率42%)を得た。
1H−NMR(CDCl3,400MHz)δ8.02(d,J=8.0Hz,1H),7.93(qd,J=2.3Hz,15.9Hz,1H),7.86(d,J=8.0Hz,2H),7.59(d,J=7.1Hz,1H),7.56−7.49(m,2H),7.45(dd,J=7.7Hz,7.7Hz,1H),6.24(qd,J=6.5Hz,15.9Hz,1H);19F−NMR(CDCl3,376MHz)δ−63.4(s,3F).
1H−NMR(CDCl3,400MHz)δ7.42−7.37(m,4H),7.13(qd,J=2.2Hz,16.1Hz,1H),6.16(qd,J=6.6Hz,16.1Hz,1H),1.32(s,9H);19F−NMR(CDCl3,376MHz)δ−63.1(s,3F).
1H−NMR(CDCl3,400MHz)δ7.37(d,J=8.6Hz,2H),7.12(qd,J=2.1Hz,16.1Hz,1H),6.89(d,J=8.6Hz,2H),6.09(qd,J=6.6Hz,16.1Hz,1H),1.03(s,9H),0.26(s,6H);19F−NMR(CDCl3,376MHz)δ−62.9(s,3F).
1H−NMR(CDCl3,400MHz)δ7.54(d,J=8.0Hz,2H),7.42(d,J=8.0Hz,2H),7.14(qd,J=2.1Hz,16.1Hz,1H),6.22(qd,J=6.6Hz,16.1Hz,1H),0.28(s,9H);19F−NMR(CDCl3,376MHz)δ−63.3(s,3F).
1H−NMR(CDCl3,400MHz)δ7.51(dd,J=2.2Hz,6.9Hz,1H),7.32(ddd,J=2.2Hz,4.4Hz,8.5Hz,1H),7.16(dd,J=8.5Hz,8.5Hz,1H),7.06(qd,J=2.2Hz,16.1Hz,1H),6.15(qd,J=6.3Hz,16.1Hz,1H);19F−NMR(CDCl3,376MHz)δ−63.6(s,3F),−112.6(s,1F).
1H−NMR(CDCl3,400MHz)δ10.46(s,1H),7.93(d,J=2.4Hz,1H),7.64(dd,J=2.4Hz,8.7Hz,1H),7.09(qd,J=2.1Hz,16.1Hz,1H),7.03(d,J=8.7Hz,1H),6.16(qd,J=6.5Hz,16.1Hz,1H),3.98(s,3H);19F−NMR(CDCl3,376MHz)δ−63.2(s,3F).
1H−NMR(CDCl3,400MHz)δ8.06(d,J=8.3Hz,2H),7.52(d,J=8.3Hz,2H),7.18(qd,J=2.0Hz,16.1Hz,1H),6.30(qd,J=6.4Hz,16.1Hz,1H),3.93(s,3H);19F−NMR(CDCl3,376MHz)δ−63.7(s,3F).
1H−NMR(CDCl3,400MHz)δ7.62−7.59(m,4H),7.51(d,J=8.2Hz,2H),7.45(dd,J=7.3Hz,7.3Hz,2H),7.37(dd,J=7.3Hz,7.3Hz,1H),7.18(qd,J=1.9Hz,16.1Hz,1H),6.23(qd,J=6.5Hz,16.1Hz,1H);19F−NMR(CDCl3,376MHz)δ−63.2(s,3F).
1H−NMR(CDCl3,400MHz)δ7.19(dd,J=7.9Hz,7.9Hz,1H),7.02(qd,J=2.1Hz,16.1Hz,1H),6.93(d,J=7.9Hz,1H),6.89−6.82(m,2H),6.09(qd,J=6.6Hz,16.1Hz,1H),3.89(t,J=6.5Hz,2H),1.73−1.66(m,2H),1.47−1.37(m,2H),0.9(t,J=7.4Hz,3H);19F−NMR(CDCl3,376MHz)δ−63.3(s,3F).
1H−NMR(CDCl3,400MHz)δ7.84−7.79(m,4H),7.63−7.48(m,5H),7.22(qd,J=2.0Hz,16.2Hz,1H),6.33(qd,J=6.4Hz,16.2Hz,1H);19F−NMR(CDCl3,376MHz)δ−63.6(s,3F).
1H−NMR(CDCl3,400MHz)δ7.50(d,J=8.3Hz,2H),7.45(d,J=8.3Hz,2H),7.16(qd,J=2.1Hz,16.1Hz,1H),6.25(qd,J=6.5Hz,16.1Hz,1H),3.12(s,3H),2.98(s,3H);19F−NMR(CDCl3,376MHz)δ−63.5(s,3F).
1H−NMR(CDCl3,400MHz)δ7.70(d,J=8.3Hz,2H),7.36(d,J=8.3Hz,2H),7.18(qd,J=2.1Hz,16.2Hz,1H),6.32(qd,J=6.4Hz,16.2Hz,1H);19F−NMR(CDCl3,376MHz)δ−63.9(s,3F).
1H−NMR(CDCl3,400MHz)δ7.84(m,4H),7.13(qd,J=2.2Hz,16.1Hz,1H),6.71(dd,J=10.9Hz,17.6Hz,1H),6.19(qd,J=6.6Hz,16.1Hz,1H),5.81(dd,J=0.6Hz,17.6Hz,1H),5.32(dd,J=0.6Hz,10.9Hz,1H);19F−NMR(CDCl3,376MHz)δ−63.2(s,3F).
1H−NMR(CDCl3,400MHz)δ7.89(s,3H),7.24(qd,J=2.2Hz,16.1Hz,1H),6.39(qd,J=6.2Hz,16.1Hz,1H);19F−NMR(CDCl3,376MHz)δ−63.2(s,3F),−64.1(s,6F).
1H−NMR(CDCl3,400MHz)δ7.29−7.26(m,6H),7.12−7.00(m,9H),6.04(qd,J=6.6Hz,15.9Hz,1H);19F−NMR(CDCl3,376MHz)δ−62.7(s,3F).
実施例−17
1H−NMR(CDCl3,400MHz)δ7.38(s,1H),7.32−7.23(m,3H),7.15(qd,J=2.1Hz,16.1Hz,1H),6.28(qd,J=6.4Hz,16.1Hz,1H),3.09(q,J=7.5Hz,2H),1.29(t,J=7.5Hz,3H);19F−NMR(CDCl3,376MHz)δ−63.4(s,3F).
1H−NMR(CDCl3,400MHz)δ8.05(s,1H),7.96(d,J=7.8Hz,1H),7.74(d,J=7.8Hz,1H),7.63(dd,J=7.8Hz,7.8Hz,1H),7.22(qd,J=2.1Hz,16.2Hz,1H),6.36(qd,J=6.3Hz,16.2Hz,1H),3.09(s,3H);19F−NMR(CDCl3,376MHz)δ−63.9(s,3F).
1H−NMR(CDCl3,400MHz)δ8.33(s,1H),8.25(d,J=8.0Hz,1H),7.79(d,J=8.0Hz,1H),7.61(dd,J=8.0Hz,8.0Hz,1H),7.23(qd,J=2.0Hz,16.1Hz,1H),6.37(qd,J=6.3Hz,16.1Hz,1H);19F−NMR(CDCl3,376MHz)δ−63.9(s,3F).
1H−NMR(CDCl3,400MHz)δ7.90(d,J=8.4Hz,2H),7.47(d,J=8.4Hz,2H),7.11(qd,J=2.1Hz,16.1Hz,1H),6.23(qd,J=6.5Hz,16.1Hz,1H),2.54(s,3H);19F−NMR(CDCl3,376MHz)δ−63.7(s,3F).
1H−NMR(CDCl3,400MHz)δ7.56(qd,J=2.2Hz,15.9Hz,1H),7.42(d,J=7.6Hz,1H),7.38−7.31(m,2H),7.21(ddd,J=1.6Hz,7.3Hz,7.3Hz,1H),6.08(qd,J=6.5Hz,15.9Hz,1H),3.21(sept,J=6.8Hz,1H),1.25(sept,J=6.8Hz,6H);19F−NMR(CDCl3,376MHz)δ−63.3(s,3F).
1H−NMR(CDCl3,400MHz)δ8.05−7.99(m,2H),7.58−7.43(m,3H),6.06(qd,J=6.4Hz,16.0Hz,1H),3.92(s,3H);19F−NMR(CDCl3,376MHz)δ−63.6(s,3F).
1H−NMR(CDCl3,400MHz)δ8.21(d,J=2.4Hz,1H),7.70(dd,J=2.4Hz,8.7Hz,1H),7.09(qd,J=2.0Hz,16.1Hz,1H),6.78(d,J=8.7Hz,1H),6.10(qd,J=6.4Hz,16.1Hz,1H)3.97(s,3H);19F−NMR(CDCl3,376MHz)δ−63.2(s,3F).
1H−NMR(CDCl3,400MHz)δ8.63(s,2H),7.07(qd,J=2.1Hz,16.3Hz,1H),6.24(qd,J=6.3Hz,16.3Hz,1H),4.06(s,3H);19F−NMR(CDCl3,376MHz)δ−63.8(s,3F).
1H−NMR(CDCl3,400MHz)δ7.21(qd,J=2.1Hz,16.5Hz,1H),6.89(s,2H),5.81(qd,J=6.4Hz,16.5Hz,1H),2.28(s,9H);19F−NMR(CDCl3,376MHz)δ−63.9(s,3F).
1H−NMR(CDCl3,400MHz)δ9.98(s,1H),7.52(s,1H),7.39(s,1H),7.20(s,1H),7.15(qd,J=2.1Hz,16.1Hz,1H),6.28(qd,J=6.4Hz,16.1Hz,1H),4.66(sep,J=6.0Hz,1H),1.38(d,J=6.0Hz,6H);19F−NMR(CDCl3,376MHz)δ−63.6(s,3F).
1H−NMR(CDCl3,400MHz)δ9.03(d,J=2.2Hz,1H),8.20(d,J=2.2Hz,1H),8.13(d,J=8.4Hz,1H),7.86(d,J=8.1Hz,1H),7.77(dd,J=6.9Hz,8.4Hz,1H),7.60(dd,J=6.9Hz,8.1Hz,1H),7.33(qd,J=2.0Hz,16.2Hz,1H),6.45(qd,J=6.3Hz,16.2Hz,1H);19F−NMR(CDCl3,376MHz)δ−63.6(s,3F).
1H−NMR(CDCl3,400MHz)δ7.46(s,1H),7.37(m,3H),7.15(qd,J=2.1Hz,16.1Hz,1H),6.22(qd,J=6.5Hz,16.1Hz,1H),4.71(s,2H),1.92(s,1H);19F−NMR(CDCl3,376MHz)δ−63.4(s,3F).
1H−NMR(CDCl3,400MHz)δ7.58(d,J=7.8Hz,1H),7.48(d,J=7.8Hz,1H),7.36(dd,J=7.8Hz,7.8Hz,1H),7.25(dd,J=7.8Hz,7.8Hz,1H),7.15(qd,J=2.1Hz,15.7Hz,1H),6.87(s,1H),6.42(qd,J=7.0Hz,15.7Hz,1H);19F−NMR(CDCl3,376MHz)δ−64.2(s,3F).
1H−NMR(CDCl3,400MHz)δ7.65(s,1H),7.32−7.23(m,2H),7.14−7.09(m,2H),6.52(s,1H),6.21(qd,J=6.5Hz,16.1Hz,1H),1.53(s,9H);19F−NMR(CDCl3,376MHz)δ−63.4(s,3F).
1H−NMR(CDCl3,400MHz)δ7.78(qd,J=2.2Hz,16.1Hz,1H),7.35(dd,J=1.5Hz,3.3Hz,1H),6.58(dd,J=1.5Hz,3.3Hz,1H),6.20(dd,J=3.3Hz,3.3Hz,1H),5.97(qd,J=6.7Hz,16.1Hz,1H),1.61(s,9H);19F−NMR(CDCl3,376MHz)δ−63.0(s,3F).
1H−NMR(CDCl3,400MHz)δ7.86−7.82(m,4H),7.59(dd,J=1.6Hz,8.6Hz,1H),7.53−7.51(m,2H),7.31(qd,J=2.0Hz,16.1Hz,1H),6.31(qd,J=6.6Hz,16.1Hz,1H);19F−NMR(CDCl3,376MHz)δ−63.1(s,3F).
トリ−tert−ブチルホスホニウムテトラフルオロボラートに替えてジシクロヘキシル(2’,4’,6’−トリイソプロピル−[1,1’−ビフェニル]−2−イル)ホスフィン4.8mg(0.01mmol)を用いた以外は全て実施例−32と同じ操作を行い、ガスクロマトグラフィーにより(E)−2−(3,3,3−トリフルオロ−1−プロペン−1−イル)ナフタレンの生成を確認した(GC収率16%)。
アルゴン雰囲気下、反応容器にナフタレン−2−イルボロン酸86mg(0.5mmol)、ジクロロ[1,1’−ビス(ジ−tert−ブチルホスフィノ)フェロセン]パラジウム3.3mg(0.005mmol)、炭酸ナトリウム10水和物286mg(1mmol)、1.5Mの(E)−1−クロロ−3,3,3−トリフルオロプロペンのテトラヒドロフラン溶液0.5mL(0.75mmol)を加えた。反応容器を密閉した後、室温で12時間攪拌した。反応後、ガスクロマトグラフィーにより(E)−2−(3,3,3−トリフルオロ−1−プロペン−1−イル)ナフタレンの生成を確認した(GC収率79%)。
アルゴン雰囲気下、反応容器にナフタレン−2−イルボロン酸86mg(0.5mmol)、トリス(ジベンジリデンアセトン)ジパラジウム2.3mg(0.0025mmol)、トリ−tert−ブチルホスホニウムテトラフルオロボラート2.9mg(0.01mmol)、フッ化カリウム58mg(1mmol)、1.5Mの(E)−1−クロロ−3,3,3−トリフルオロプロペンのテトラヒドロフラン溶液0.5mL(0.75mmol)、テトラヒドロフラン0.5mL及び蒸留水0.36mLを加えた。反応容器を密閉した後、60℃で12時間攪拌した。反応後、ガスクロマトグラフィーにより(E)−2−(3,3,3−トリフルオロ−1−プロペン−1−イル)ナフタレンの生成を確認した(GC収率75%)。
水を加えなかった以外は全て実施例−34と同じ操作を行い、ガスクロマトグラフィーにより(E)−2−(3,3,3−トリフルオロ−1−プロペン−1−イル)ナフタレンの生成を確認した(GC収率10%)。
アルゴン雰囲気下、反応容器にナフタレン−2−イルボロン酸86mg(0.5mmol)、トリス(ジベンジリデンアセトン)ジパラジウム2.3mg(0.0025mmol)、トリ−tert−ブチルホスホニウムテトラフルオロボラート2.9mg(0.01mmol)、炭酸カリウム138mg(1mmol)、1.5Mの(E)−1−クロロ−3,3,3−トリフルオロプロペンのテトラヒドロフラン溶液0.5mL(0.75mmol)、テトラヒドロフラン0.5mL及び蒸留水0.36mLを加えた。反応容器を密閉した後、60℃で1時間攪拌した。反応後、ガスクロマトグラフィーにより(E)−2−(3,3,3−トリフルオロ−1−プロペン−1−イル)ナフタレンの生成を確認した(GC収率72%)。
炭酸カリウムに替えて炭酸水素ナトリウム84mg(1mmol)を用いた以外は全て実施例−34と同じ操作を行い、ガスクロマトグラフィーにより(E)−2−(1−プロペン−1−イル)ナフタレンの生成を確認した(GC収率74%)。
アルゴン雰囲気下、反応容器にナフタレン−2−イルボロン酸86mg(0.5mmol)、塩化パラジウム0.9mg(0.005mmol)、トリ−tert−ブチルホスホニウムテトラフルオロボラート2.9mg(0.01mmol)、炭酸ナトリウム10水和物286mg(1mmol)、1.5Mの(E)−1−クロロ−3,3,3−トリフルオロプロペンのテトラヒドロフラン溶液0.5mL(0.75mmol)、テトラヒドロフラン0.5mL及び蒸留水0.18mLを加えた。反応容器を密閉した後、60℃で3時間攪拌した。反応後、ガスクロマトグラフィーにより(E)−2−(3,3,3−トリフルオロ−1−プロペン−1−イル)ナフタレンの生成を確認した(GC収率64%)。
塩化パラジウムに替えてビス(アセチルアセトナト)パラジウム1.5mg(0.005mmol)を用いた以外は全て実施例−36と同じ操作を行い、ガスクロマトグラフィーにより(E)−2−(1−プロペン−1−イル)ナフタレンの生成を確認した(GC収率70%)。
塩化パラジウムに替えてジクロロビス(ベンゾニトリル)パラジウム1.9mg(0.005mmol)を用いた以外は全て実施例−36と同じ操作を行い、ガスクロマトグラフィーにより(E)−2−(1−プロペン−1−イル)ナフタレンの生成を確認した(GC収率72%)。
アルゴン雰囲気下、反応容器にナフタレン−2−イルボロン酸86mg(0.5mmol)、トリス(ジベンジリデンアセトン)ジパラジウム2.3mg(0.0025mmol)、トリ−tert−ブチルホスホニウムテトラフルオロボラート2.9mg(0.01mmol)、炭酸セシウム326mg(1mmol)、1.5Mの(E)−1−クロロ−3,3,3−トリフルオロプロペンのテトラヒドロフラン溶液0.5mL(0.75mmol)、テトラヒドロフラン0.5mL及び蒸留水0.36mLを加えた。反応容器を密閉した後、60℃で3時間攪拌した。反応後、ガスクロマトグラフィーにより(E)−2−(3,3,3−トリフルオロ−1−プロペン−1−イル)ナフタレンの生成を確認した(GC収率88%)。
炭酸セシウムに替えてリン酸カリウム212mg(1mmol)を用いた以外は全て実施例−39と同じ操作を行い、ガスクロマトグラフィーにより(E)−2−(1−プロペン−1−イル)ナフタレンの生成を確認した(GC収率99%)。
アルゴン雰囲気下、反応容器にナフタレン−2−イルボロン酸86mg(0.5mmol)、トリス(ジベンジリデンアセトン)ジパラジウム2.3mg(0.0025mmol)、トリ−tert−ブチルホスホニウムテトラフルオロボラート2.9mg(0.01mmol)、フッ化セシウム152mg(1mmol)、1.5Mの(E)−1−クロロ−3,3,3−トリフルオロプロペンのテトラヒドロフラン溶液0.5mL(0.75mmol)、テトラヒドロフラン0.5mL及び蒸留水0.18mLを加えた。反応容器を密閉した後、60℃で3時間攪拌した。反応後、ガスクロマトグラフィーにより(E)−2−(3,3,3−トリフルオロ−1−プロペン−1−イル)ナフタレンの生成を確認した(GC収率97%)。
フッ化セシウムに替えて8Mの水酸化ナトリウム溶液0.125mL(1mmol)を用いた以外は全て実施例−41と同じ操作を行い、ガスクロマトグラフィーにより(E)−2−(1−プロペン−1−イル)ナフタレンの生成を確認した(GC収率74%)。
1H−NMR(CDCl3,400MHz)δ7.99(d,J=8.4Hz,2H),7.36(d,J=8.4Hz,2H),7.21(s,1H),3.91(s,3H),2.36(t,J=7.2Hz,2H),1.48−1.29(m,16H),0.87(t,J=7.2Hz,3H).
1H−NMR(CDCl3,400MHz)δ8.04(d,J=8.4Hz,2H),7.35(d,J=8.4Hz,2H),6.85(qd,J=1.6Hz,16.0Hz,1H),6.72(s,1H),5.81(qd,J=6.6Hz,16.0Hz,1H),3.93(s,3H),2.43(t,J=8.0Hz,2H),1.53−1.31(m,4H),0.93(t,J=7.28Hz,3H);19F−NMR(CDCl3,376MHz)δ−62.8(s,3F).
1H−NMR(CDCl3,400MHz)δ7.30−7.28(m,2H),7.09(d,J=3.6Hz,1H),7.00(dd,J=5.0Hz,3.6Hz,1H),3.68(s,4H),2.48(t,J=7.4Hz,2H),1.45−1.40(m,4H),0.99(s,6H),0.94(t,J=7.0Hz,3H).
1H−NMR(CDCl3,400MHz)δδ7.39(d,J=5.1Hz.1H),7.12(d,J=3.6Hz,1H),7.07(dd,J=5.1Hz,3.6Hz,1H),6.84−6.79(m、2H),5.72(qd、J=6.8Hz,15.9Hz,1H),2.57(t、J=8.0Hz,2H),1.51−1.49(m、4H),0.99(t,J=6.9Hz,3H);19F−NMR(CDCl3,376MHz)δ−62.3(s,3F).
1H−NMR(CDCl3,400MHz)δ6.27(t,J=7.1Hz,1H),2.13−2.08(m,4H),1.42−1.25(m,24H),0.88(t,J=6.9Hz,3H),0.87(t,J=6.9Hz,3H).
1H−NMR(CDCl3,400MHz)δ6.66(qd、J=1.9Hz,16.0Hz,1H),5.73(t、J=7.4Hz,1H),5.55(qd、J=6.8Hz,16.0Hz,1H),2.21−2.12(m,4H),1.44−1.29(m、12H),0.90(t,J=7.0Hz,3H)0.89(t,J=7.0Hz,3H);19F−NMR(CDCl3,376MHz)δ−62.4(s,3F).
1H−NMR(CDCl3,400MHz)δ7.36(s,1H),7.28−7.04(m,10H),1.31(s,12H).
1H−NMR(CDCl3,400MHz)δ7.46−7.39(m,3H),7.18−7.11(m,6H),6.94−6.92(m,2H),6.83(s,1H),5.28(qd,J=7.1Hz,15.5Hz,1H);19F−NMR(CDCl3,376MHz)δ−62.7(s,3F).
1H−NMR(CDCl3,400MHz)δ8.19(d,J=8.8Hz,2H),7.43(d,J=8.8Hz,2H),7.21(s,1H),2.35(t,J=7.3Hz,2H),1.48−1.27(m,16H),0.88(t,J=7.2Hz,3H).
1H−NMR(CDCl3,400MHz)δ8.24(d,J=8.8Hz,2H),7.44(d,J=8.8Hz,2H),6.85(qd,J=1.4Hz,16.0Hz,1H),6.73(s,1H),5.87(qd,J=6.5Hz,16.0Hz,1H),2.43(t,J=8.3Hz,2H),1.56−1.35(m,4H),0.94(t,J=7.3Hz,3H);19F−NMR(CDCl3,376MHz)δ−63.0(s,3F).
1H−NMR(CDCl3,400MHz)δ7.92(d,J=8.2Hz,2H),7.39(d,J=8.2Hz,2H),7.21(s,1H),2.37(t,J=7.6Hz,2H),1.49−1.29(m,16H),0.88(t,J=7.2Hz,3H).
1H−NMR(CDCl3,400MHz)δ7.97(d,J=8.4Hz,2H),7.39(d,J=8.4Hz,2H),6.85(qd,J=1.6Hz,16.0Hz,1H),6.72(s,1H),5.82(qd,J=6.6Hz,16.0Hz,1H),2.62(s,3H),2.44(t,J=8.4Hz,2H),1.54−1.35(m,4H),0.94(t,J=7.3Hz,3H);19F−NMR(CDCl3,376MHz)δ−62.8(s,3F).
1H−NMR(CDCl3,400MHz)δ7.64(d,J=7.6Hz,1H),7.47(d,J=7.6Hz,1H),7.36−7.32(m,2H),7.26(d,J=7.6Hz,1H),2.12(t,J=7.6Hz,2H),1.4−1.14(m,16H),0.80(t,J=7.3Hz,3H);19F−NMR(CDCl3,376MHz)δ−60.9(s,3F).
1H−NMR(CDCl3,400MHz)δ7.69(d,J=7.7Hz,1H),7.54(dd,J=7.7Hz,7.7Hz,1H),7.41(dd,J=7.7Hz,7.7Hz,1H),7.30(d,J=7.7Hz,1H),6.89−6.83(m,2H),5.81(qd,J=6.5Hz,16.1Hz,1H),2.25(t,J=8.1Hz,2H),1.45−1.20(m,4H),0.82(t,J=7.3Hz,3H);19F−NMR(CDCl3,376MHz)δ−62.9(s,3F),−60.3(s,3F).
1H−NMR(CDCl3,400MHz)δ7.61(d,J=8.2Hz,2H),7.38(d,J=8.2Hz,2H),7.16(s,1H),2.32(t,J=7.4Hz,2H),1.47−1.26(m,16H),0.87(t,J=7.2Hz,3H).
1H−NMR(CDCl3,400MHz)δ7.67(d,J=8.4Hz,2H),7.38(d,J=8.4Hz,2H),6.84(qd,J=1.6Hz,16.0Hz,1H),6.68(s,1H),5.84(qd,J=6.6Hz,16.0Hz,1H),2.40(t,J=8.0Hz,2H),1.53−1.34(m,4H),0.93(t,J=7.2Hz,3H);19F−NMR(CDCl3,376MHz)δ−62.9(s,3F).
1H−NMR(CDCl3,400MHz)δ7.24(t,J=8.0Hz,1H),7.17(s,1H),6.91(d,J=8.0Hz,1H),6.88(s,1H),6.79(d,J=8.0Hz,1H),3.79(s,3H),2.38(t,J=7.2Hz,2H),1.49−1.26(m,16H),0.88(t,J=7.2Hz,3H).
1H−NMR(CDCl3,400MHz)δ7.29(dd,J=7.7Hz,9.0Hz,1H),6.89(d,J=7.7Hz,1H),6.86−6.81(m,3H),6.68(s,1H),5.76(qd,J=6.6Hz,15.8Hz,1H),3.82(s,3H),2.44(t,J=8.3Hz,2H),1.57−1.35(m,4H),0.94(t,J=7.3Hz,3H);19F−NMR(CDCl3,376MHz)δ−62.6(s,3F).
1H−NMR(CDCl3,400MHz)δ7.29(s,1H),7.25−7.16(m,3H),7.12(s,1H),2.34(t,J=7.4Hz,2H),1.46−1.28(m,16H),0.88(t,J=7.2Hz,3H).
1H−NMR(CDCl3,400MHz)δ7.33−7.27(m,3H),7.16(d,J=7.3Hz,1H),6.82(qd,J=1.6Hz,16.0Hz,1H),6.63(s,1H),5.79(qd,J=6.6Hz,16.0Hz,1H),2.41(t,J=8.3Hz,2H),1.56−1.36(m,4H),0.94(t,J=7.3Hz,3H);19F−NMR(CDCl3,376MHz)δ−62.8(s,3F).
1H−NMR(CDCl3,400MHz)δ7.26(d,J=7.4Hz,1H),7.22(d,J=7.4Hz,1H),7.18(s,1H),7.10−7.01(m,2H),2.27(t,J=7.6Hz,2H),1.46−1.23(m,16H),0.84(t,J=7.3Hz,3H);19F−NMR(CDCl3,376MHz)δ−114.2(s,1F).
1H−NMR(CDCl3,400MHz)δ7.31−7.26(m,2H),7.16−7.05(m,2H),6.87(qd,J=1.6Hz,16.0Hz,1H),6.73(s,1H),5.79(qd,J=6.6Hz,16.0Hz,1H),2.38(t,J=8.3Hz,2H),1.53−1.29(m,4H),0.89(t,J=7.3Hz,3H);19F−NMR(CDCl3,376MHz)δ−62.8(s,3F),−113.9(s,1F).
Claims (8)
- 一般式(1)
(式中、Rfは炭素数1から4のフルオロアルキル基を示す。)で表される1−クロロ−2−(フルオロアルキル)エチレンと一般式(2)
(式中、Xはジヒドロキシボリル基、メチル基で置換されていてもよい1,3,2−ジオキサボロラン−2−イル基、またはメチル基で置換されていてもよい1,3,2−ジオキサボリナン−2−イル基を示す。Rはナフタレン−1−イル基、ナフタレン−2−イル基、キノリン−3−イル基、ベンゾフラン−2−イル基、1−tert−ブトキシカルボニル−1H−ピロール−2−イル基、一般式(3)
(式中、R1は水素原子、フッ素原子、塩素原子、炭素数1から8のアルキル基、炭素数1から4のハロアルキル基、炭素数2から6のアルケニル基、炭素数1から8のアルキルオキシ基、トリ(炭素数1から4のアルキル)シリル基、トリ(炭素数1から4のアルキル)シリルオキシ基、炭素数1から6のアルキルチオ基、炭素数1から4のアルキルスルホニル基、炭素数1から5のアシル基、(炭素数1から4のアルキルオキシ)カルボニル基、(炭素数1から4のアルキルオキシ)カルボニルアミノ基、(炭素数2から8のジアルキルアミノ)カルボニル基、ベンジルオキシ基、フェニル基、ベンゾイル基、ジフェニルアミノ基、ヒドロキシメチル基、シアノ基またはニトロ基を示す。複数のR1は同一または相異なっていてもよい。Zは窒素原子、または、同一または相異なったR1が置換した炭素原子を示す。複数のZは同一または相異なっていてもよい。)で表される6員環芳香族基、または一般式(4)
(式中、R2は炭素数1から8のアルキル基またはフェニル基を示す。R3は炭素数1から4のアルキルオキシ基、炭素数2から5のアシル基、(炭素数1から4のアルキルオキシ)カルボニル基、炭素数1から4のフルオロアルキル基、塩素原子、シアノ基またはニトロ基で置換されていてもよいフェニル基、炭素数1から8のアルキル基またはチオフェン−2−イル基を示す。)で表されるビニル基を示す。)で表される有機ホウ素化合物を、アルキルホスフィン配位パラジウム触媒とアルカリ金属塩及び水の共存下で反応させることを特徴とする、一般式(5)
(式中、Rf及びRは、前記と同じ内容を示す。)で表される一置換(フルオロアルキル)エチレン類の製造方法。 - 水が有機ホウ素化合物(2)に対して10〜100モル当量である請求項1に記載の製造方法。
- アルキルホスフィン配位パラジウム触媒が、パラジウム化合物とアルキルホスフィン化合物から調製した触媒である請求項1または2に記載の製造方法。
- アルキルホスフィン化合物が、トリ−tert−ブチルホスフィン、トリ−tert−ブチルホスホニウムテトラフルオロボラートまたは1,1’−ビス(ジ−tert−ブチルホスフィノ)フェロセンである請求項3に記載の製造方法;
- アルキルホスフィン配位パラジウム触媒が、ジクロロ[1,1’−ビス(ジ−tert−ブチルホスフィノ)フェロセン]パラジウムである請求項1または2に記載の製造方法。
- アルカリ金属塩が炭酸アルカリ金属塩、炭酸水素アルカリ金属塩、フッ化アルカリ金属塩、水酸化アルカリ金属塩またはリン酸アルカリ金属塩である請求項1から5のいずれかに記載の製造方法。
- アルカリ金属塩がナトリウム、カリウムまたはセシウム塩である請求項1から6のいずれかに記載の製造方法。
- Rfがトリフルオロメチル基である請求項1から7のいずれかに記載の製造方法。
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