JP2011148779A - 2−クロロ−3−トリフルオロメチルピリジンの製造方法 - Google Patents
2−クロロ−3−トリフルオロメチルピリジンの製造方法 Download PDFInfo
- Publication number
- JP2011148779A JP2011148779A JP2010284115A JP2010284115A JP2011148779A JP 2011148779 A JP2011148779 A JP 2011148779A JP 2010284115 A JP2010284115 A JP 2010284115A JP 2010284115 A JP2010284115 A JP 2010284115A JP 2011148779 A JP2011148779 A JP 2011148779A
- Authority
- JP
- Japan
- Prior art keywords
- trifluoromethylpyridine
- chloro
- oxide
- chlorinating agent
- solution
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- RXATZPCCMYMPME-UHFFFAOYSA-N 2-chloro-3-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CC=CN=C1Cl RXATZPCCMYMPME-UHFFFAOYSA-N 0.000 title claims abstract description 32
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 20
- GBXKHNRJGRFFGG-UHFFFAOYSA-N 1-oxido-3-(trifluoromethyl)pyridin-1-ium Chemical compound [O-][N+]1=CC=CC(C(F)(F)F)=C1 GBXKHNRJGRFFGG-UHFFFAOYSA-N 0.000 claims abstract description 29
- 239000012320 chlorinating reagent Substances 0.000 claims abstract description 23
- 238000000034 method Methods 0.000 claims abstract description 10
- 150000003839 salts Chemical class 0.000 claims abstract description 10
- JTZSFNHHVULOGJ-UHFFFAOYSA-N 3-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CC=CN=C1 JTZSFNHHVULOGJ-UHFFFAOYSA-N 0.000 claims abstract description 9
- 238000006243 chemical reaction Methods 0.000 claims description 35
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 claims description 22
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 12
- 230000001590 oxidative effect Effects 0.000 abstract description 3
- 239000003905 agrochemical Substances 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract description 2
- 229940079593 drug Drugs 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 45
- 239000000243 solution Substances 0.000 description 45
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 10
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 238000004811 liquid chromatography Methods 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 239000002585 base Substances 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- 238000001035 drying Methods 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- -1 sulfonic acid chlorides Chemical class 0.000 description 5
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 4
- 239000005457 ice water Substances 0.000 description 4
- 239000011259 mixed solution Substances 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 4
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 3
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 239000007800 oxidant agent Substances 0.000 description 3
- OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 description 2
- ATRQECRSCHYSNP-UHFFFAOYSA-N 2-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CC=CC=N1 ATRQECRSCHYSNP-UHFFFAOYSA-N 0.000 description 2
- XRXANEMIFVRKLN-UHFFFAOYSA-N 2-hydroperoxy-2-methylbutane Chemical compound CCC(C)(C)OO XRXANEMIFVRKLN-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 229940117389 dichlorobenzene Drugs 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 150000008282 halocarbons Chemical class 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 2
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 235000010265 sodium sulphite Nutrition 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- PZHIWRCQKBBTOW-UHFFFAOYSA-N 1-ethoxybutane Chemical compound CCCCOCC PZHIWRCQKBBTOW-UHFFFAOYSA-N 0.000 description 1
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 1
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 1
- YNJSNEKCXVFDKW-UHFFFAOYSA-N 3-(5-amino-1h-indol-3-yl)-2-azaniumylpropanoate Chemical compound C1=C(N)C=C2C(CC(N)C(O)=O)=CNC2=C1 YNJSNEKCXVFDKW-UHFFFAOYSA-N 0.000 description 1
- WMCGGHPSLQFUDV-UHFFFAOYSA-N 3-(fluoromethyl)pyridine Chemical compound FCC1=CC=CN=C1 WMCGGHPSLQFUDV-UHFFFAOYSA-N 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- RGUKYNXWOWSRET-UHFFFAOYSA-N 4-pyrrolidin-1-ylpyridine Chemical compound C1CCCN1C1=CC=NC=C1 RGUKYNXWOWSRET-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- YQHLDYVWEZKEOX-UHFFFAOYSA-N cumene hydroperoxide Chemical compound OOC(C)(C)C1=CC=CC=C1 YQHLDYVWEZKEOX-UHFFFAOYSA-N 0.000 description 1
- GGSUCNLOZRCGPQ-UHFFFAOYSA-N diethylphenylamine Natural products CCN(CC)C1=CC=CC=C1 GGSUCNLOZRCGPQ-UHFFFAOYSA-N 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- HCUYBXPSSCRKRF-UHFFFAOYSA-N diphosgene Chemical compound ClC(=O)OC(Cl)(Cl)Cl HCUYBXPSSCRKRF-UHFFFAOYSA-N 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- HPFQJBOXPBNOJK-UHFFFAOYSA-N ethyl 1-oxidopyridin-1-ium-3-carboxylate Chemical compound CCOC(=O)C1=CC=C[N+]([O-])=C1 HPFQJBOXPBNOJK-UHFFFAOYSA-N 0.000 description 1
- PMIMPBYTPPRBGD-UHFFFAOYSA-N ethyl 2-chloropyridine-3-carboxylate Chemical compound CCOC(=O)C1=CC=CN=C1Cl PMIMPBYTPPRBGD-UHFFFAOYSA-N 0.000 description 1
- 238000005755 formation reaction Methods 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 150000002432 hydroperoxides Chemical class 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- YKYONYBAUNKHLG-UHFFFAOYSA-N n-Propyl acetate Natural products CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 description 1
- PPHQUIPUBYPZLD-UHFFFAOYSA-N n-ethyl-n-methylaniline Chemical compound CCN(C)C1=CC=CC=C1 PPHQUIPUBYPZLD-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 150000004965 peroxy acids Chemical class 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- 239000003880 polar aprotic solvent Substances 0.000 description 1
- 235000011056 potassium acetate Nutrition 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
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
- 229940090181 propyl acetate Drugs 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- YMBCJWGVCUEGHA-UHFFFAOYSA-M tetraethylammonium chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC YMBCJWGVCUEGHA-UHFFFAOYSA-M 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- PVFOMCVHYWHZJE-UHFFFAOYSA-N trichloroacetyl chloride Chemical compound ClC(=O)C(Cl)(Cl)Cl PVFOMCVHYWHZJE-UHFFFAOYSA-N 0.000 description 1
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
- RKBCYCFRFCNLTO-UHFFFAOYSA-N triisopropylamine Chemical compound CC(C)N(C(C)C)C(C)C RKBCYCFRFCNLTO-UHFFFAOYSA-N 0.000 description 1
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/61—Halogen atoms or nitro radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4402—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 2, e.g. pheniramine, bisacodyl
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4453—Non condensed piperidines, e.g. piperocaine only substituted in position 1, e.g. propipocaine, diperodon
Abstract
【解決手段】 3−トリフルオロメチルピリジン N−オキシドと塩素化剤とを反応させることを特徴とする、2−クロロ−3−トリフルオロメチルピリジン又はその塩の製造方法、また、3−トリフルオロメチルピリジンを酸化して3−トリフルオロメチルピリジン N−オキシドを製造し、次いでこのものと塩素化剤とを反応させることを特徴とする、2−クロロ−3−トリフルオロメチルピリジン又はその塩の製造方法。
【選択図】 なし
Description
非特許文献1には、3−エトキシカルボニルピリジン N−オキシドとオキシ塩化リンとを反応させて2−クロロ−3−ピリジンカルボン酸エチルを製造する方法が記載されているが、2−クロロ−3−トリフルオロメチルピリジンの製造方法については記載されていない。
即ち本発明は、3−トリフルオロメチルピリジン N−オキシドと塩素化剤とを反応させることを特徴とする、2−クロロ−3−トリフルオロメチルピリジン又はその塩の製造方法、また、3−トリフルオロメチルピリジンを酸化して3−トリフルオロメチルピリジン N−オキシドを製造し、次いでこのものと塩素化剤とを反応させることを特徴とする、2−クロロ−3−トリフルオロメチルピリジン又はその塩の製造方法に関する。
また、塩基を用いる場合、任意の順序で添加することができ、例えば塩素化剤を添加する前又は後に添加しても、それと同時に添加してもよい。塩基を用いる場合、塩素化剤を添加した後に塩基を添加すると、2−クロロ−3−トリフルオロメチルピリジンを製造する上でその生成率、収率が顕著に向上する。
実施例1
(1)攪拌器、温度計及び冷却管を備えた四ツ口フラスコに、3−トリフルオロメチルピリジン147.0gと酢酸367.75gを仕込んだ。そこへ20〜30℃で30%過酸化水素水141.71gを投入し、80〜90℃で7時間反応させた。
反応液を冷却後、30℃以下で亜硫酸ナトリウム31.51gを添加した。添加後30〜40℃で3時間攪拌し、反応液中の過剰の過酸化水素の処理が完了していることをヨウ化カリウムデンプン紙により確認した。
反応液を減圧下(15mmHg)で内温が50℃に達するまで加熱し、酢酸を留去した。そこへ水441mLを投入し、20℃以下で30%水酸化ナトリウム水溶液204.26gを滴下し、pH8.0に調整した。その後、1,2−ジクロロエタン275.6gによる保温抽出を50℃で3回繰り返し、3−トリフルオロメチルピリジン N−オキシド(融点76.0℃)158.16gを含む1,2−ジクロロエタン溶液985.0gを得た。
反応液を10℃以下で氷水24.45gに投入し、10〜20℃で30分間攪拌した後分液した。得られた有機層を水洗し、2-クロロ−3−トリフルオロメチルピリジンを含む1,2−ジクロロエタン溶液43.1gを得た。得られた溶液を液体クロマトグラフィーで分析し、当該溶液中に2-クロロ−3−トリフルオロメチルピリジン4.25gを含むことを確認した。
攪拌器、温度計及び乾燥管を備えた四ツ口フラスコに、3−トリフルオロメチルピリジン N−オキシド32.62gとオキシ塩化リン46.0gを仕込み、105〜110℃で2時間反応させ、次いで120〜125℃で5時間さらに反応させた。反応液を液体クロマトグラフィーで分析し、3−トリフルオロメチルピリジン N−オキシドを0.16%、2−クロロ−3−トリフルオロメチルピリジンを50.34%、2−クロロ−5−トリフルオロメチルピリジンを25.34%の割合で含むことを確認した。
反応液を減圧下(100mmHg)で内温が75℃に達するまで加熱し、過剰分のオキシ塩化リンを留去した。反応液を氷水163.1gに投入し、30℃以下で1時間攪拌した。その後、1,2−ジクロロエタンで抽出し、30分間攪拌して分液した。得られた有機層を水洗し、2−クロロ−3−トリフルオロメチルピリジンを含む1,2−ジクロロエタン溶液132.11gを得た。得られた溶液を液体クロマトグラフィーで分析し、当該溶液中に2−クロロ−3−トリフルオロメチルピリジン13.17gを含むことを確認した。
(1)攪拌器、温度計及び冷却管を備えた四ツ口フラスコに、3−トリフルオロメチルピリジン238.63gと酢酸596.57gを仕込んだ。そこへ20〜30℃で30%過酸化水素水229.85gを投入し、80〜90℃で7時間反応させた。
反応液を冷却後、30℃以下で亜硫酸ナトリウム51.11gを添加した。添加後30〜40℃で3時間攪拌し、反応液中の過剰の過酸化水素の処理が完了していることをヨウ化カリウムデンプン紙により確認した。
反応液を減圧下(15mmHg)で内温が55℃に達するまで加熱し、酢酸を留去した。そこへ水357.9mLを投入し、15℃以下で30%水酸化ナトリウム水溶液343.2gを滴下し、pH8.0に調整した。その後、ジクロロメタン633.1gによる保温抽出を30〜40℃で2回繰り返した。次に、ジクロロメタン抽出溶液を常圧下で内温が50℃に達するまで加熱してジクロロメタンを留去すると共に系内の水分を除去し、3−トリフルオロメチルピリジン N−オキシド(融点76.0℃)259.57gを含むジクロロメタン溶液811.9gを得た。
反応液を10℃以下で氷水1019.3gに投入し、10〜20℃で1時間攪拌した後分液した。得られた有機層に水407.8gを投入し、20〜30℃で30%水酸化ナトリウム水溶液26.7gを滴下してpH8.0に調整し、同温度で2時間攪拌した。その後、分液し2-クロロ−3−トリフルオロメチルピリジンを含むジクロロメタン溶液1531gを得た。得られた溶液から常圧でジクロロメタンを留去し、内温が90℃に到達するまで加熱した後、減圧下(38mmHg)で内温が100℃に到達するまでの留分を収集して、純度99.27%の2-クロロ−3−トリフルオロメチルピリジン161.27gを得た。
攪拌器、温度計、乾燥管及び滴下漏斗を備えた四ツ口フラスコに、3−トリフルオロメチルピリジン N−オキシド3.26gを含む1,2−ジクロロエタン溶液23.65g(13.78%溶液)を仕込んだ。そこへ0〜5℃で塩化オキサリル3.05gを滴下し、同温度で1時間反応させた。反応液に、0〜10℃でトリエチルアミン2.42g及び1,2−ジクロロエタン4.08gの混合溶液を1時間要して滴下し、同温度で2時間さらに反応させた。反応液を液体クロマトグラフィーで分析し、3−トリフルオロメチルピリジン N−オキシドを39.72%、2−クロロ−3−トリフルオロメチルピリジンを54.63%、2−クロロ−5−トリフルオロメチルピリジンを1.31%の割合で含むことを確認した。
攪拌器、温度計、乾燥管及び滴下漏斗を備えた四ツ口フラスコに、3−トリフルオロメチルピリジン N−オキシド16.31gを含むジクロロメタン溶液124.49g(13.10%溶液)を仕込んだ。そこへ−30〜−20℃で塩化オキサリル12.69gを滴下し、同温度で1時間反応させた。反応液に、−30〜−20℃でトリエチルアミン10.12g及びジクロロメタン10.82gの混合溶液を1時間要して滴下し、同温度で2時間さらに反応させた。反応液を液体クロマトグラフィーで分析し、3−トリフルオロメチルピリジン N−オキシドを5.47%、2−クロロ−3−トリフルオロメチルピリジンを85.57%、2−クロロ−5−トリフルオロメチルピリジンを0.42%の割合で含むことを確認した。
反応液を10℃以下で氷水81.55gに投入し、10〜20℃で1時間攪拌した後分液した。得られた有機層を水洗し、2-クロロ−3−トリフルオロメチルピリジンを含むジクロロメタン溶液143.25gを得た。得られた溶液を液体クロマトグラフィーで分析し、当該溶液中に2-クロロ−3−トリフルオロメチルピリジン14.18gを含むことを確認した。
Claims (6)
- 3−トリフルオロメチルピリジン N−オキシドと塩素化剤とを反応させることを特徴とする、2−クロロ−3−トリフルオロメチルピリジン又はその塩の製造方法。
- 3−トリフルオロメチルピリジンを酸化して3−トリフルオロメチルピリジン N−オキシドを製造し、次いでこのものと塩素化剤とを反応させることを特徴とする、2−クロロ−3−トリフルオロメチルピリジン又はその塩の製造方法。
- 塩素化剤が塩化オキサリル及びオキシ塩化リンからなる群より選ばれる少なくとも1種である請求項1又は2の方法。
- 塩素化剤が塩化オキサリルである請求項1又は2の方法。
- 3−トリフルオロメチルピリジン N−オキシド1モルに対し、塩素化剤を1〜10倍モル使用する請求項1又は2の方法。
- 3−トリフルオロメチルピリジン N−オキシドと塩素化剤との反応を、塩素化剤として塩化オキサリルを用い、−40℃〜20℃の反応温度で行う、請求項1又は2の方法。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2010284115A JP5702595B2 (ja) | 2009-12-25 | 2010-12-21 | 2−クロロ−3−トリフルオロメチルピリジンの製造方法 |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2009293768 | 2009-12-25 | ||
JP2009293768 | 2009-12-25 | ||
JP2010284115A JP5702595B2 (ja) | 2009-12-25 | 2010-12-21 | 2−クロロ−3−トリフルオロメチルピリジンの製造方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2011148779A true JP2011148779A (ja) | 2011-08-04 |
JP5702595B2 JP5702595B2 (ja) | 2015-04-15 |
Family
ID=44195821
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2010284115A Active JP5702595B2 (ja) | 2009-12-25 | 2010-12-21 | 2−クロロ−3−トリフルオロメチルピリジンの製造方法 |
Country Status (8)
Country | Link |
---|---|
US (1) | US8691997B2 (ja) |
EP (1) | EP2520569B1 (ja) |
JP (1) | JP5702595B2 (ja) |
KR (1) | KR101668144B1 (ja) |
CN (1) | CN102712590B (ja) |
BR (1) | BR112012015701B1 (ja) |
IL (1) | IL220520A (ja) |
WO (1) | WO2011078296A1 (ja) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103601671B (zh) * | 2013-10-22 | 2016-08-17 | 上海泰坦科技股份有限公司 | 碘代三氟甲基吡啶的制备方法 |
EP4105202B1 (en) * | 2018-01-05 | 2024-05-01 | Zhejiang Lantian Environmental Protection Hi-Tech Co., Ltd. | Method for preparing 2-chloro-5-trifluoromethylpyridine |
CN108409643A (zh) * | 2018-02-07 | 2018-08-17 | 南京红太阳生物化学有限责任公司 | 一种2-氯-3-三氯甲基吡啶的合成方法 |
CN113717095A (zh) * | 2021-07-15 | 2021-11-30 | 山东汇盟生物科技股份有限公司 | 一种制备2-氯-3-三氟甲基吡啶和2-氯-5-三氟甲基吡啶的方法 |
CN115784977A (zh) * | 2023-02-06 | 2023-03-14 | 淄博新农基作物科学有限公司 | 2-氯-3-三氟甲基吡啶的合成工艺 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5581860A (en) * | 1978-12-07 | 1980-06-20 | Ici Ltd | Chlorination |
JPS55122762A (en) * | 1979-03-16 | 1980-09-20 | Ishihara Sangyo Kaisha Ltd | Production of chloro-3-trifluoromethylpyridine |
JPS5659757A (en) * | 1979-10-22 | 1981-05-23 | Ishihara Sangyo Kaisha Ltd | Preparation of 2-chloro-5-trifluoromethylpyridine |
JPH0948759A (ja) * | 1981-05-13 | 1997-02-18 | Imperial Chem Ind Plc <Ici> | 3−トリフルオロメチルピリジンの製造方法 |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0013474B1 (en) | 1978-12-07 | 1983-06-29 | Imperial Chemical Industries Plc | Preparation of 2-chloro-5-trifluoromethylpyridine |
DE3800179A1 (de) | 1988-01-07 | 1989-07-20 | Bayer Ag | Verfahren zur herstellung von 2-chlor-5-methyl-pyridin |
JP3291345B2 (ja) | 1993-01-27 | 2002-06-10 | 広栄化学工業株式会社 | 2−クロロ−3−シアノピリジンの製造法 |
EP3412290B1 (en) * | 2006-03-27 | 2021-03-03 | The Regents of The University of California | Androgen receptor modulator for the treatment of prostate cancer and androgen receptor-associated diseases |
JP2009293768A (ja) | 2008-06-09 | 2009-12-17 | Bridgestone Corp | ストラットマウント |
-
2010
- 2010-12-21 JP JP2010284115A patent/JP5702595B2/ja active Active
- 2010-12-22 US US13/518,584 patent/US8691997B2/en active Active
- 2010-12-22 BR BR112012015701-9A patent/BR112012015701B1/pt active IP Right Grant
- 2010-12-22 KR KR1020127015827A patent/KR101668144B1/ko active IP Right Grant
- 2010-12-22 CN CN201080059179.8A patent/CN102712590B/zh active Active
- 2010-12-22 EP EP10839526.0A patent/EP2520569B1/en active Active
- 2010-12-22 WO PCT/JP2010/073252 patent/WO2011078296A1/ja active Application Filing
-
2012
- 2012-06-19 IL IL220520A patent/IL220520A/en active IP Right Grant
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5581860A (en) * | 1978-12-07 | 1980-06-20 | Ici Ltd | Chlorination |
US4393214A (en) * | 1978-12-07 | 1983-07-12 | Imperial Chemical Industries Plc | Preparation of 2-chloro-5-trifluoromethylpyridine and 2-chloro-5-perchlorofluoromethylpyridines |
JPS55122762A (en) * | 1979-03-16 | 1980-09-20 | Ishihara Sangyo Kaisha Ltd | Production of chloro-3-trifluoromethylpyridine |
JPS5659757A (en) * | 1979-10-22 | 1981-05-23 | Ishihara Sangyo Kaisha Ltd | Preparation of 2-chloro-5-trifluoromethylpyridine |
JPH0948759A (ja) * | 1981-05-13 | 1997-02-18 | Imperial Chem Ind Plc <Ici> | 3−トリフルオロメチルピリジンの製造方法 |
Also Published As
Publication number | Publication date |
---|---|
EP2520569A4 (en) | 2013-06-05 |
IL220520A (en) | 2016-05-31 |
IL220520A0 (en) | 2012-08-30 |
KR101668144B1 (ko) | 2016-10-20 |
CN102712590B (zh) | 2014-04-30 |
US8691997B2 (en) | 2014-04-08 |
EP2520569A1 (en) | 2012-11-07 |
BR112012015701A2 (pt) | 2015-09-15 |
JP5702595B2 (ja) | 2015-04-15 |
CN102712590A (zh) | 2012-10-03 |
US20120259125A1 (en) | 2012-10-11 |
EP2520569B1 (en) | 2014-03-26 |
BR112012015701B1 (pt) | 2021-04-20 |
WO2011078296A1 (ja) | 2011-06-30 |
KR20120120171A (ko) | 2012-11-01 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5702595B2 (ja) | 2−クロロ−3−トリフルオロメチルピリジンの製造方法 | |
KR101421862B1 (ko) | 함질소 복소 고리 화합물 및 그 제조 방법 | |
TWI695824B (zh) | 製備3-氯-2-乙烯基苯基磺酸酯之方法 | |
US9518019B2 (en) | Process for the preparation of 4-amino-5-fluoro-3-chloro-6-(substituted)picolinates | |
JP6614699B2 (ja) | 有害生物防除剤の製造方法およびその中間体 | |
CN110520411A (zh) | 吡啶化合物的制造方法 | |
JP2009235062A (ja) | 3−アミノ−2−クロロ−6−トリフルオロメチルピリジンの製造方法 | |
AU2015281846B2 (en) | Method for manufacturing 3-(alkyl sulfonyl)pyridine-2-carboxylic acid | |
JP2016084346A (ja) | ビス(3−フェネチルオキシフェニル)ジスルフィド誘導体およびその製造方法 | |
JP4698991B2 (ja) | ピリジルメチルカルバミン酸エステル化合物、その製造方法及びピリジルメチルアミン化合物の製造方法 | |
JPH09132565A (ja) | 3−(置換アミノメチル)−6−クロロピリジン及びその製造方法 | |
JP2013129616A (ja) | 臭素化剤及びその利用 | |
TW201726624A (zh) | 2-胺基菸鹼酸苄酯衍生物之製造方法 | |
JP2017114787A (ja) | ピリジン化合物の製造方法 | |
JPH08217753A (ja) | 2−クロロ−3−シアノピリジンの製造方法 | |
JP2007246476A (ja) | ジオキサジニルピラゾール化合物の製造方法および中間体 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20131202 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20140930 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20141112 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20150217 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20150220 |
|
R151 | Written notification of patent or utility model registration |
Ref document number: 5702595 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R151 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |