NO318854B1 - Fremgangsmate for fremstilling av 2-fenyl-3-naftylpropionsyrederivater - Google Patents
Fremgangsmate for fremstilling av 2-fenyl-3-naftylpropionsyrederivater Download PDFInfo
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- NO318854B1 NO318854B1 NO19991098A NO991098A NO318854B1 NO 318854 B1 NO318854 B1 NO 318854B1 NO 19991098 A NO19991098 A NO 19991098A NO 991098 A NO991098 A NO 991098A NO 318854 B1 NO318854 B1 NO 318854B1
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- mmol
- formula
- mixture
- ethyl ester
- oxy
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- 238000000034 method Methods 0.000 title claims description 95
- 238000002360 preparation method Methods 0.000 title claims description 27
- ZMOGIZHWBARKJF-UHFFFAOYSA-N 3-naphthalen-1-yl-2-phenylpropanoic acid Chemical class C=1C=CC2=CC=CC=C2C=1CC(C(=O)O)C1=CC=CC=C1 ZMOGIZHWBARKJF-UHFFFAOYSA-N 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims description 131
- 239000000203 mixture Substances 0.000 claims description 104
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 101
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 57
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical group [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 40
- 238000006243 chemical reaction Methods 0.000 claims description 40
- 239000012312 sodium hydride Substances 0.000 claims description 40
- 229910000104 sodium hydride Inorganic materials 0.000 claims description 40
- 239000002585 base Substances 0.000 claims description 25
- 239000002904 solvent Substances 0.000 claims description 25
- 150000003839 salts Chemical class 0.000 claims description 23
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 14
- 238000004519 manufacturing process Methods 0.000 claims description 14
- 239000002798 polar solvent Substances 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 8
- 125000006239 protecting group Chemical group 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
- 125000005843 halogen group Chemical group 0.000 claims description 6
- 238000005658 halogenation reaction Methods 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
- 229910000102 alkali metal hydride Inorganic materials 0.000 claims description 5
- 150000008046 alkali metal hydrides Chemical group 0.000 claims description 5
- 239000011877 solvent mixture Substances 0.000 claims description 5
- 238000000605 extraction Methods 0.000 claims description 4
- 239000011541 reaction mixture Substances 0.000 claims description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 60
- FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical compound CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 42
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 41
- 239000000047 product Substances 0.000 description 39
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 37
- 238000004458 analytical method Methods 0.000 description 35
- VMWIZZARXXSROL-UHFFFAOYSA-N 7-(bromomethyl)naphthalene-2-carbonitrile Chemical compound C1=CC(C#N)=CC2=CC(CBr)=CC=C21 VMWIZZARXXSROL-UHFFFAOYSA-N 0.000 description 33
- 239000013078 crystal Substances 0.000 description 33
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 30
- DULCUDSUACXJJC-UHFFFAOYSA-N Ethyl phenylacetate Chemical compound CCOC(=O)CC1=CC=CC=C1 DULCUDSUACXJJC-UHFFFAOYSA-N 0.000 description 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 29
- 239000012044 organic layer Substances 0.000 description 28
- -1 aromatic amidine Chemical class 0.000 description 26
- 230000002829 reductive effect Effects 0.000 description 25
- 229910052739 hydrogen Inorganic materials 0.000 description 24
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 24
- 238000003756 stirring Methods 0.000 description 24
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 20
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 16
- HYUPPKVFCGIMDB-UHFFFAOYSA-N ethyl 2-(4-hydroxyphenyl)acetate Chemical compound CCOC(=O)CC1=CC=C(O)C=C1 HYUPPKVFCGIMDB-UHFFFAOYSA-N 0.000 description 15
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 14
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- NVVGPZRNNSWGRA-CYZZXXEPSA-N ethyl 2-[4-[(3s)-1-benzylpyrrolidin-3-yl]oxyphenyl]-3-(7-cyanonaphthalen-2-yl)propanoate Chemical compound C([C@@H](C1)OC2=CC=C(C=C2)C(CC=2C=C3C=C(C=CC3=CC=2)C#N)C(=O)OCC)CN1CC1=CC=CC=C1 NVVGPZRNNSWGRA-CYZZXXEPSA-N 0.000 description 12
- 238000001704 evaporation Methods 0.000 description 11
- 230000002411 adverse Effects 0.000 description 10
- 238000010898 silica gel chromatography Methods 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- XEJYIXSQJAMFDO-UHFFFAOYSA-N 7-methylnaphthalene-2-carbonitrile Chemical compound C1=CC(C#N)=CC2=CC(C)=CC=C21 XEJYIXSQJAMFDO-UHFFFAOYSA-N 0.000 description 7
- 230000008020 evaporation Effects 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- 239000000543 intermediate Substances 0.000 description 7
- 239000003960 organic solvent Substances 0.000 description 7
- YFNKIDBQEZZDLK-UHFFFAOYSA-N triglyme Chemical compound COCCOCCOCCOC YFNKIDBQEZZDLK-UHFFFAOYSA-N 0.000 description 7
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 150000001298 alcohols Chemical class 0.000 description 6
- 150000002170 ethers Chemical class 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 6
- KWQRKOSMSFLBTJ-MRVPVSSYSA-N tert-butyl (3r)-3-methylsulfonyloxypyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC[C@@H](OS(C)(=O)=O)C1 KWQRKOSMSFLBTJ-MRVPVSSYSA-N 0.000 description 6
- 229910052783 alkali metal Inorganic materials 0.000 description 5
- 238000009835 boiling Methods 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 230000026030 halogenation Effects 0.000 description 5
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 5
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 5
- XQXPVVBIMDBYFF-UHFFFAOYSA-N 4-hydroxyphenylacetic acid Chemical class OC(=O)CC1=CC=C(O)C=C1 XQXPVVBIMDBYFF-UHFFFAOYSA-N 0.000 description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 238000000862 absorption spectrum Methods 0.000 description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 4
- 238000000921 elemental analysis Methods 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 239000003999 initiator Substances 0.000 description 4
- 229910052740 iodine Inorganic materials 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 239000003444 phase transfer catalyst Substances 0.000 description 4
- 230000035484 reaction time Effects 0.000 description 4
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical class [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- NZIDTDIDEPGKHB-GFCCVEGCSA-N [(3r)-1-benzylpyrrolidin-3-yl] methanesulfonate Chemical compound C1[C@H](OS(=O)(=O)C)CCN1CC1=CC=CC=C1 NZIDTDIDEPGKHB-GFCCVEGCSA-N 0.000 description 3
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 3
- 150000008041 alkali metal carbonates Chemical class 0.000 description 3
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 3
- KVNRLNFWIYMESJ-UHFFFAOYSA-N butyronitrile Chemical compound CCCC#N KVNRLNFWIYMESJ-UHFFFAOYSA-N 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- NVVGPZRNNSWGRA-ACHIHNKUSA-N ethyl (2s)-2-[4-[(3s)-1-benzylpyrrolidin-3-yl]oxyphenyl]-3-(7-cyanonaphthalen-2-yl)propanoate Chemical compound C([C@@H](C1)OC2=CC=C(C=C2)[C@H](CC=2C=C3C=C(C=CC3=CC=2)C#N)C(=O)OCC)CN1CC1=CC=CC=C1 NVVGPZRNNSWGRA-ACHIHNKUSA-N 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- LRDFRRGEGBBSRN-UHFFFAOYSA-N isobutyronitrile Chemical compound CC(C)C#N LRDFRRGEGBBSRN-UHFFFAOYSA-N 0.000 description 3
- JILPJDVXYVTZDQ-UHFFFAOYSA-N lithium methoxide Chemical compound [Li+].[O-]C JILPJDVXYVTZDQ-UHFFFAOYSA-N 0.000 description 3
- AZVCGYPLLBEUNV-UHFFFAOYSA-N lithium;ethanolate Chemical compound [Li+].CC[O-] AZVCGYPLLBEUNV-UHFFFAOYSA-N 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- 239000008096 xylene Substances 0.000 description 3
- CSDQQAQKBAQLLE-UHFFFAOYSA-N 4-(4-chlorophenyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine Chemical compound C1=CC(Cl)=CC=C1C1C(C=CS2)=C2CCN1 CSDQQAQKBAQLLE-UHFFFAOYSA-N 0.000 description 2
- UQNGUWMXNDNMEG-UHFFFAOYSA-N 7-(chloromethyl)naphthalene-2-carbonitrile Chemical compound C1=CC(C#N)=CC2=CC(CCl)=CC=C21 UQNGUWMXNDNMEG-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- 102100029117 Coagulation factor X Human genes 0.000 description 2
- 108010014173 Factor X Proteins 0.000 description 2
- RJUFJBKOKNCXHH-UHFFFAOYSA-N Methyl propionate Chemical compound CCC(=O)OC RJUFJBKOKNCXHH-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
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 206010040880 Skin irritation Diseases 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 150000001342 alkaline earth metals Chemical class 0.000 description 2
- 230000031709 bromination Effects 0.000 description 2
- 238000005893 bromination reaction Methods 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 229940105756 coagulation factor x Drugs 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 125000004494 ethyl ester group Chemical group 0.000 description 2
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 125000001153 fluoro group Chemical group F* 0.000 description 2
- 230000002140 halogenating effect Effects 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- SIAPCJWMELPYOE-UHFFFAOYSA-N lithium hydride Chemical compound [LiH] SIAPCJWMELPYOE-UHFFFAOYSA-N 0.000 description 2
- 229910000103 lithium hydride Inorganic materials 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 150000004714 phosphonium salts Chemical class 0.000 description 2
- 239000003586 protic polar solvent Substances 0.000 description 2
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 230000036556 skin irritation Effects 0.000 description 2
- 231100000475 skin irritation Toxicity 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- UCGVCNQTLHGDDL-LBAUFKAWSA-N tert-butyl (3s)-2-[4-(2-ethoxy-2-oxoacetyl)phenoxy]-3-hydroxypyrrolidine-1-carboxylate Chemical compound C1=CC(C(=O)C(=O)OCC)=CC=C1OC1N(C(=O)OC(C)(C)C)CC[C@@H]1O UCGVCNQTLHGDDL-LBAUFKAWSA-N 0.000 description 2
- NMJRXFTUIGIPII-MBMZGMDYSA-N tert-butyl (3s)-3-[4-[3-(7-cyanonaphthalen-2-yl)-1-ethoxy-1-oxopropan-2-yl]phenoxy]pyrrolidine-1-carboxylate Chemical compound C=1C=C2C=CC(C#N)=CC2=CC=1CC(C(=O)OCC)C(C=C1)=CC=C1O[C@H]1CCN(C(=O)OC(C)(C)C)C1 NMJRXFTUIGIPII-MBMZGMDYSA-N 0.000 description 2
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- YMHNNMWDCPDSGJ-UHFFFAOYSA-N (7-cyanonaphthalen-2-yl)methyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OCC1=CC=C(C=CC(=C2)C#N)C2=C1 YMHNNMWDCPDSGJ-UHFFFAOYSA-N 0.000 description 1
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-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
- OCYJXSUPZMNXEN-UHFFFAOYSA-N 2-amino-1-(4-nitrophenyl)propane-1,3-diol Chemical compound OCC(N)C(O)C1=CC=C([N+]([O-])=O)C=C1 OCYJXSUPZMNXEN-UHFFFAOYSA-N 0.000 description 1
- SBUZVHKAMPSVDL-UHFFFAOYSA-N 2-phenyl-2-pyrrolidin-1-yloxyacetic acid Chemical class C=1C=CC=CC=1C(C(=O)O)ON1CCCC1 SBUZVHKAMPSVDL-UHFFFAOYSA-N 0.000 description 1
- KUAPFVDTEQJNKF-UHFFFAOYSA-N 3-(3-phenylnaphthalen-2-yl)propanoic acid Chemical class OC(=O)CCC1=CC2=CC=CC=C2C=C1C1=CC=CC=C1 KUAPFVDTEQJNKF-UHFFFAOYSA-N 0.000 description 1
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
- VHOMAPWVLKRQAZ-UHFFFAOYSA-N Benzyl propionate Chemical compound CCC(=O)OCC1=CC=CC=C1 VHOMAPWVLKRQAZ-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- SSMBXPJYHMZLOJ-UHFFFAOYSA-N Isopropyl phenylacetate Chemical compound CC(C)OC(=O)CC1=CC=CC=C1 SSMBXPJYHMZLOJ-UHFFFAOYSA-N 0.000 description 1
- IJMWOMHMDSDKGK-UHFFFAOYSA-N Isopropyl propionate Chemical compound CCC(=O)OC(C)C IJMWOMHMDSDKGK-UHFFFAOYSA-N 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- CRZQGDNQQAALAY-UHFFFAOYSA-N Methyl benzeneacetate Chemical compound COC(=O)CC1=CC=CC=C1 CRZQGDNQQAALAY-UHFFFAOYSA-N 0.000 description 1
- 238000006751 Mitsunobu reaction Methods 0.000 description 1
- RFFFKMOABOFIDF-UHFFFAOYSA-N Pentanenitrile Chemical compound CCCCC#N RFFFKMOABOFIDF-UHFFFAOYSA-N 0.000 description 1
- MIYFJEKZLFWKLZ-UHFFFAOYSA-N Phenylmethyl benzeneacetate Chemical compound C=1C=CC=CC=1COC(=O)CC1=CC=CC=C1 MIYFJEKZLFWKLZ-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 238000007239 Wittig reaction Methods 0.000 description 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 230000002429 anti-coagulating effect Effects 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- RCISCZVMZIEKPN-UHFFFAOYSA-L barium(2+) sulfate hydrate Chemical compound O.[Ba+2].[O-]S([O-])(=O)=O RCISCZVMZIEKPN-UHFFFAOYSA-L 0.000 description 1
- 235000019400 benzoyl peroxide Nutrition 0.000 description 1
- VBQDSLGFSUGBBE-UHFFFAOYSA-N benzyl(triethyl)azanium Chemical compound CC[N+](CC)(CC)CC1=CC=CC=C1 VBQDSLGFSUGBBE-UHFFFAOYSA-N 0.000 description 1
- HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N benzyl-alpha-carboxylic acid Natural products OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 230000000711 cancerogenic effect Effects 0.000 description 1
- 229950005499 carbon tetrachloride Drugs 0.000 description 1
- 231100000357 carcinogen Toxicity 0.000 description 1
- 239000003183 carcinogenic agent Substances 0.000 description 1
- 238000011097 chromatography purification Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 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
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 1
- DZSXZYDBNQVSMU-UHFFFAOYSA-N ethyl 2-(4-hydroxyphenyl)-2-oxoacetate Chemical compound CCOC(=O)C(=O)C1=CC=C(O)C=C1 DZSXZYDBNQVSMU-UHFFFAOYSA-N 0.000 description 1
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- SDAXRHHPNYTELL-UHFFFAOYSA-N heptanenitrile Chemical compound CCCCCCC#N SDAXRHHPNYTELL-UHFFFAOYSA-N 0.000 description 1
- AILKHAQXUAOOFU-UHFFFAOYSA-N hexanenitrile Chemical compound CCCCCC#N AILKHAQXUAOOFU-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 238000009776 industrial production Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 125000005948 methanesulfonyloxy group Chemical group 0.000 description 1
- XGDZEDRBLVIUMX-UHFFFAOYSA-N methyl 2-(4-hydroxyphenyl)acetate Chemical compound COC(=O)CC1=CC=C(O)C=C1 XGDZEDRBLVIUMX-UHFFFAOYSA-N 0.000 description 1
- 229940017219 methyl propionate Drugs 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 description 1
- 230000014508 negative regulation of coagulation Effects 0.000 description 1
- HBEQXAKJSGXAIQ-UHFFFAOYSA-N oxopalladium Chemical compound [Pd]=O HBEQXAKJSGXAIQ-UHFFFAOYSA-N 0.000 description 1
- 229910003445 palladium oxide Inorganic materials 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 229960003424 phenylacetic acid Drugs 0.000 description 1
- 239000003279 phenylacetic acid Substances 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- AMVCMHXBGWPOTF-UHFFFAOYSA-N sulfane;tetrabutylazanium Chemical compound S.CCCC[N+](CCCC)(CCCC)CCCC AMVCMHXBGWPOTF-UHFFFAOYSA-N 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- MWACHFODPQVXHF-CYBMUJFWSA-N tert-butyl (3r)-3-(4-methylphenyl)sulfonyloxypyrrolidine-1-carboxylate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)O[C@H]1CN(C(=O)OC(C)(C)C)CC1 MWACHFODPQVXHF-CYBMUJFWSA-N 0.000 description 1
- RUPAXCPQAAOIPB-UHFFFAOYSA-N tert-butyl formate Chemical group CC(C)(C)OC=O RUPAXCPQAAOIPB-UHFFFAOYSA-N 0.000 description 1
- JAELLLITIZHOGQ-UHFFFAOYSA-N tert-butyl propanoate Chemical compound CCC(=O)OC(C)(C)C JAELLLITIZHOGQ-UHFFFAOYSA-N 0.000 description 1
- NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 1
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 1
- HWCKGOZZJDHMNC-UHFFFAOYSA-M tetraethylammonium bromide Chemical compound [Br-].CC[N+](CC)(CC)CC HWCKGOZZJDHMNC-UHFFFAOYSA-M 0.000 description 1
- CMSYDJVRTHCWFP-UHFFFAOYSA-N triphenylphosphane;hydrobromide Chemical compound Br.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 CMSYDJVRTHCWFP-UHFFFAOYSA-N 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/49—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C255/50—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton to carbon atoms of non-condensed six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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
- C07D207/12—Oxygen or sulfur atoms
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyrrole Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP23701496 | 1996-09-06 | ||
| JP23701396 | 1996-09-06 | ||
| JP5735797 | 1997-03-12 | ||
| PCT/JP1997/003125 WO1998009945A1 (fr) | 1996-09-06 | 1997-09-05 | Procede pour la preparation de derives d'acide 2-phenyl-3-naphtylpropionique |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO991098D0 NO991098D0 (no) | 1999-03-05 |
| NO991098L NO991098L (no) | 1999-05-05 |
| NO318854B1 true NO318854B1 (no) | 2005-05-18 |
Family
ID=27296228
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19991098A NO318854B1 (no) | 1996-09-06 | 1999-03-05 | Fremgangsmate for fremstilling av 2-fenyl-3-naftylpropionsyrederivater |
Country Status (9)
| Country | Link |
|---|---|
| US (3) | US6252088B1 (ko) |
| EP (1) | EP0936215A4 (ko) |
| KR (2) | KR100514806B1 (ko) |
| CN (4) | CN1241913C (ko) |
| AU (1) | AU725497B2 (ko) |
| CA (1) | CA2264933A1 (ko) |
| NO (1) | NO318854B1 (ko) |
| TW (1) | TW430652B (ko) |
| WO (1) | WO1998009945A1 (ko) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW430652B (en) * | 1996-09-06 | 2001-04-21 | Daiichi Seiyaku Co | Process for preparing 2-phenyl-3-naphthyl propionic acid derivatives |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6227971A (ja) * | 1985-07-31 | 1987-02-05 | 伊藤超短波株式会社 | 医療用レ−ザ装置 |
| ZA928276B (en) * | 1991-10-31 | 1993-05-06 | Daiichi Seiyaku Co | Aromatic amidine derivates and salts thereof. |
| JP3457694B2 (ja) * | 1993-02-04 | 2003-10-20 | 第一製薬株式会社 | インフルエンザ感染予防・治療薬 |
| JP3406644B2 (ja) * | 1993-07-06 | 2003-05-12 | 第一製薬株式会社 | ナフタレン誘導体の製造方法及び製造中間体 |
| TW430652B (en) * | 1996-09-06 | 2001-04-21 | Daiichi Seiyaku Co | Process for preparing 2-phenyl-3-naphthyl propionic acid derivatives |
-
1997
- 1997-09-04 TW TW086112753A patent/TW430652B/zh not_active IP Right Cessation
- 1997-09-05 US US09/147,785 patent/US6252088B1/en not_active Expired - Fee Related
- 1997-09-05 CN CNB021302510A patent/CN1241913C/zh not_active Expired - Fee Related
- 1997-09-05 CN CNA021302529A patent/CN1535955A/zh active Pending
- 1997-09-05 CA CA002264933A patent/CA2264933A1/en not_active Abandoned
- 1997-09-05 WO PCT/JP1997/003125 patent/WO1998009945A1/ja not_active Application Discontinuation
- 1997-09-05 KR KR10-2004-7016957A patent/KR100514806B1/ko not_active IP Right Cessation
- 1997-09-05 CN CN97198579A patent/CN1104415C/zh not_active Expired - Fee Related
- 1997-09-05 EP EP97939188A patent/EP0936215A4/en not_active Withdrawn
- 1997-09-05 AU AU41354/97A patent/AU725497B2/en not_active Ceased
- 1997-09-05 KR KR10-1999-7001886A patent/KR100491673B1/ko not_active IP Right Cessation
-
1999
- 1999-03-05 NO NO19991098A patent/NO318854B1/no unknown
-
2000
- 2000-12-22 US US09/742,348 patent/US6337405B1/en not_active Expired - Fee Related
-
2001
- 2001-11-07 US US09/986,075 patent/US6515142B2/en not_active Expired - Fee Related
-
2002
- 2002-08-21 CN CN02130250A patent/CN1446796A/zh active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| KR20000068485A (ko) | 2000-11-25 |
| CN1535954A (zh) | 2004-10-13 |
| CN1232449A (zh) | 1999-10-20 |
| NO991098D0 (no) | 1999-03-05 |
| CA2264933A1 (en) | 1998-03-12 |
| CN1535955A (zh) | 2004-10-13 |
| KR100491673B1 (ko) | 2005-05-27 |
| EP0936215A1 (en) | 1999-08-18 |
| NO991098L (no) | 1999-05-05 |
| KR100514806B1 (ko) | 2005-09-13 |
| US6337405B1 (en) | 2002-01-08 |
| TW430652B (en) | 2001-04-21 |
| WO1998009945A1 (fr) | 1998-03-12 |
| US20020062033A1 (en) | 2002-05-23 |
| CN1241913C (zh) | 2006-02-15 |
| KR20040097379A (ko) | 2004-11-17 |
| CN1446796A (zh) | 2003-10-08 |
| AU4135497A (en) | 1998-03-26 |
| AU725497B2 (en) | 2000-10-12 |
| US6515142B2 (en) | 2003-02-04 |
| CN1104415C (zh) | 2003-04-02 |
| EP0936215A4 (en) | 2002-10-30 |
| US6252088B1 (en) | 2001-06-26 |
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