CH651288A5 - Verfahren zur herstellung von hydratropsaeurederivaten. - Google Patents
Verfahren zur herstellung von hydratropsaeurederivaten. Download PDFInfo
- Publication number
- CH651288A5 CH651288A5 CH9120/80A CH912080A CH651288A5 CH 651288 A5 CH651288 A5 CH 651288A5 CH 9120/80 A CH9120/80 A CH 9120/80A CH 912080 A CH912080 A CH 912080A CH 651288 A5 CH651288 A5 CH 651288A5
- Authority
- CH
- Switzerland
- Prior art keywords
- formula
- compound
- groups
- acid
- alkyl
- Prior art date
Links
- 238000004519 manufacturing process Methods 0.000 title description 14
- 150000001875 compounds Chemical class 0.000 claims description 83
- 239000000203 mixture Substances 0.000 claims description 67
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 61
- 238000000034 method Methods 0.000 claims description 58
- -1 aralkoxy Chemical group 0.000 claims description 41
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 37
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 34
- 239000005977 Ethylene Substances 0.000 claims description 34
- 238000002360 preparation method Methods 0.000 claims description 30
- 239000002253 acid Substances 0.000 claims description 25
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 claims description 25
- 239000002904 solvent Substances 0.000 claims description 24
- 239000003054 catalyst Substances 0.000 claims description 22
- 230000008569 process Effects 0.000 claims description 22
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 20
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 16
- 235000010288 sodium nitrite Nutrition 0.000 claims description 15
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 12
- 239000010949 copper Substances 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 11
- QMMRZOWCJAIUJA-UHFFFAOYSA-L nickel dichloride Chemical compound Cl[Ni]Cl QMMRZOWCJAIUJA-UHFFFAOYSA-L 0.000 claims description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 10
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 10
- 229910021586 Nickel(II) chloride Inorganic materials 0.000 claims description 9
- 229910052802 copper Inorganic materials 0.000 claims description 9
- 125000003118 aryl group Chemical group 0.000 claims description 8
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 8
- 239000007787 solid Substances 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 7
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
- 125000001153 fluoro group Chemical group F* 0.000 claims description 7
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 7
- 229910001623 magnesium bromide Inorganic materials 0.000 claims description 7
- 229910052751 metal Inorganic materials 0.000 claims description 7
- 239000002184 metal Substances 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 6
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical class C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 6
- 239000011777 magnesium Substances 0.000 claims description 6
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 claims description 6
- RILZRCJGXSFXNE-UHFFFAOYSA-N 2-[4-(trifluoromethoxy)phenyl]ethanol Chemical compound OCCC1=CC=C(OC(F)(F)F)C=C1 RILZRCJGXSFXNE-UHFFFAOYSA-N 0.000 claims description 5
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 claims description 5
- 229910052749 magnesium Inorganic materials 0.000 claims description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 4
- 125000004429 atom Chemical group 0.000 claims description 4
- 239000000460 chlorine Substances 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 4
- 239000011737 fluorine Substances 0.000 claims description 4
- FRIJBUGBVQZNTB-UHFFFAOYSA-M magnesium;ethane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C FRIJBUGBVQZNTB-UHFFFAOYSA-M 0.000 claims description 4
- BMGNSKKZFQMGDH-FDGPNNRMSA-L nickel(2+);(z)-4-oxopent-2-en-2-olate Chemical compound [Ni+2].C\C([O-])=C\C(C)=O.C\C([O-])=C\C(C)=O BMGNSKKZFQMGDH-FDGPNNRMSA-L 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims description 3
- 125000004414 alkyl thio group Chemical group 0.000 claims description 3
- 150000002815 nickel Chemical class 0.000 claims description 3
- 239000007864 aqueous solution Substances 0.000 claims description 2
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 2
- 125000005110 aryl thio group Chemical group 0.000 claims description 2
- 125000004104 aryloxy group Chemical group 0.000 claims description 2
- 239000003638 chemical reducing agent Substances 0.000 claims description 2
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 2
- 125000000623 heterocyclic group Chemical group 0.000 claims description 2
- 150000007942 carboxylates Chemical class 0.000 claims 2
- 125000005234 alkyl aluminium group Chemical group 0.000 claims 1
- 125000004659 aryl alkyl thio group Chemical group 0.000 claims 1
- 150000001555 benzenes Chemical class 0.000 claims 1
- 150000004292 cyclic ethers Chemical class 0.000 claims 1
- 125000005366 cycloalkylthio group Chemical group 0.000 claims 1
- 125000004663 dialkyl amino group Chemical group 0.000 claims 1
- 125000002541 furyl group Chemical group 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- UQPSGBZICXWIAG-UHFFFAOYSA-L nickel(2+);dibromide;trihydrate Chemical compound O.O.O.Br[Ni]Br UQPSGBZICXWIAG-UHFFFAOYSA-L 0.000 claims 1
- PXHVJJICTQNCMI-OUBTZVSYSA-N nickel-60 atom Chemical compound [60Ni] PXHVJJICTQNCMI-OUBTZVSYSA-N 0.000 claims 1
- 125000005936 piperidyl group Chemical group 0.000 claims 1
- 125000004076 pyridyl group Chemical group 0.000 claims 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims 1
- 125000001422 pyrrolinyl group Chemical group 0.000 claims 1
- 125000000168 pyrrolyl group Chemical group 0.000 claims 1
- 125000001544 thienyl group Chemical group 0.000 claims 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 57
- 239000000243 solution Substances 0.000 description 49
- 238000006243 chemical reaction Methods 0.000 description 48
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 43
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 42
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 34
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 32
- 239000000047 product Substances 0.000 description 23
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 22
- 239000007789 gas Substances 0.000 description 21
- 238000005859 coupling reaction Methods 0.000 description 18
- 239000011541 reaction mixture Substances 0.000 description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 238000004587 chromatography analysis Methods 0.000 description 15
- 238000005893 bromination reaction Methods 0.000 description 14
- KXUHSQYYJYAXGZ-UHFFFAOYSA-N isobutylbenzene Chemical compound CC(C)CC1=CC=CC=C1 KXUHSQYYJYAXGZ-UHFFFAOYSA-N 0.000 description 14
- 230000031709 bromination Effects 0.000 description 13
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 13
- SYTBZMRGLBWNTM-UHFFFAOYSA-N flurbiprofen Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-UHFFFAOYSA-N 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- BVBHVVRVSMBCPW-UHFFFAOYSA-N 1-bromo-4-(2-methylpropyl)benzene Chemical compound CC(C)CC1=CC=C(Br)C=C1 BVBHVVRVSMBCPW-UHFFFAOYSA-N 0.000 description 11
- 239000003795 chemical substances by application Substances 0.000 description 11
- 239000007858 starting material Substances 0.000 description 11
- GZRMNMGWNKSANY-UHFFFAOYSA-N 4-bromo-2-fluoroaniline Chemical compound NC1=CC=C(Br)C=C1F GZRMNMGWNKSANY-UHFFFAOYSA-N 0.000 description 10
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 10
- 229960000583 acetic acid Drugs 0.000 description 10
- 238000002474 experimental method Methods 0.000 description 10
- 239000007788 liquid Substances 0.000 description 10
- 239000002002 slurry Substances 0.000 description 10
- FTZQXOJYPFINKJ-UHFFFAOYSA-N 2-fluoroaniline Chemical compound NC1=CC=CC=C1F FTZQXOJYPFINKJ-UHFFFAOYSA-N 0.000 description 9
- HTRNHWBOBYFTQF-UHFFFAOYSA-N 4-bromo-2-fluoro-1-phenylbenzene Chemical group FC1=CC(Br)=CC=C1C1=CC=CC=C1 HTRNHWBOBYFTQF-UHFFFAOYSA-N 0.000 description 9
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 9
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- CODNYICXDISAEA-UHFFFAOYSA-N bromine monochloride Chemical compound BrCl CODNYICXDISAEA-UHFFFAOYSA-N 0.000 description 9
- 229960002390 flurbiprofen Drugs 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 239000004215 Carbon black (E152) Substances 0.000 description 8
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 8
- 150000007513 acids Chemical class 0.000 description 8
- 238000009835 boiling Methods 0.000 description 8
- 229930195733 hydrocarbon Natural products 0.000 description 8
- 150000002430 hydrocarbons Chemical class 0.000 description 8
- 229910052740 iodine Inorganic materials 0.000 description 8
- 239000012074 organic phase Substances 0.000 description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
- 239000007818 Grignard reagent Substances 0.000 description 7
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical class [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 7
- AZFNGPAYDKGCRB-XCPIVNJJSA-M [(1s,2s)-2-amino-1,2-diphenylethyl]-(4-methylphenyl)sulfonylazanide;chlororuthenium(1+);1-methyl-4-propan-2-ylbenzene Chemical compound [Ru+]Cl.CC(C)C1=CC=C(C)C=C1.C1=CC(C)=CC=C1S(=O)(=O)[N-][C@@H](C=1C=CC=CC=1)[C@@H](N)C1=CC=CC=C1 AZFNGPAYDKGCRB-XCPIVNJJSA-M 0.000 description 7
- 239000012298 atmosphere Substances 0.000 description 7
- 230000008901 benefit Effects 0.000 description 7
- 238000010168 coupling process Methods 0.000 description 7
- 239000012299 nitrogen atmosphere Substances 0.000 description 7
- 239000004304 potassium nitrite Substances 0.000 description 7
- 235000010289 potassium nitrite Nutrition 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 6
- 238000010521 absorption reaction Methods 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- VRLDVERQJMEPIF-UHFFFAOYSA-N dbdmh Chemical compound CC1(C)N(Br)C(=O)N(Br)C1=O VRLDVERQJMEPIF-UHFFFAOYSA-N 0.000 description 6
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 6
- 150000004795 grignard reagents Chemical class 0.000 description 6
- OWFXIOWLTKNBAP-UHFFFAOYSA-N isoamyl nitrite Chemical compound CC(C)CCON=O OWFXIOWLTKNBAP-UHFFFAOYSA-N 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- GHMLBKRAJCXXBS-UHFFFAOYSA-N resorcinol Chemical compound OC1=CC=CC(O)=C1 GHMLBKRAJCXXBS-UHFFFAOYSA-N 0.000 description 6
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 239000008346 aqueous phase Substances 0.000 description 5
- 229910052794 bromium Inorganic materials 0.000 description 5
- 238000000605 extraction Methods 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- HJQLGKFRJIWWAT-UHFFFAOYSA-N 1-bromo-2-(2-methylpropyl)benzene Chemical compound CC(C)CC1=CC=CC=C1Br HJQLGKFRJIWWAT-UHFFFAOYSA-N 0.000 description 4
- AKCRQHGQIJBRMN-UHFFFAOYSA-N 2-chloroaniline Chemical compound NC1=CC=CC=C1Cl AKCRQHGQIJBRMN-UHFFFAOYSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 229910014265 BrCl Inorganic materials 0.000 description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 4
- ATHHXGZTWNVVOU-UHFFFAOYSA-N N-methylformamide Chemical compound CNC=O ATHHXGZTWNVVOU-UHFFFAOYSA-N 0.000 description 4
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 4
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 4
- 150000003863 ammonium salts Chemical class 0.000 description 4
- DAMJCWMGELCIMI-UHFFFAOYSA-N benzyl n-(2-oxopyrrolidin-3-yl)carbamate Chemical compound C=1C=CC=CC=1COC(=O)NC1CCNC1=O DAMJCWMGELCIMI-UHFFFAOYSA-N 0.000 description 4
- 239000006227 byproduct Substances 0.000 description 4
- 229910002092 carbon dioxide Inorganic materials 0.000 description 4
- JXTHNDFMNIQAHM-UHFFFAOYSA-N dichloroacetic acid Chemical compound OC(=O)C(Cl)Cl JXTHNDFMNIQAHM-UHFFFAOYSA-N 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 4
- 229910052753 mercury Inorganic materials 0.000 description 4
- VBTQNRFWXBXZQR-UHFFFAOYSA-N n-bromoacetamide Chemical compound CC(=O)NBr VBTQNRFWXBXZQR-UHFFFAOYSA-N 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 239000000376 reactant Substances 0.000 description 4
- PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 3
- NLESZJUUVXZAAH-UHFFFAOYSA-N 4-bromo-2-chloro-1-phenylbenzene Chemical group ClC1=CC(Br)=CC=C1C1=CC=CC=C1 NLESZJUUVXZAAH-UHFFFAOYSA-N 0.000 description 3
- INMZDDDQLHKGPF-UHFFFAOYSA-N 4-bromo-2-chloroaniline Chemical compound NC1=CC=C(Br)C=C1Cl INMZDDDQLHKGPF-UHFFFAOYSA-N 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- 239000006286 aqueous extract Substances 0.000 description 3
- 150000005347 biaryls Chemical group 0.000 description 3
- 150000001649 bromium compounds Chemical class 0.000 description 3
- 239000001569 carbon dioxide Substances 0.000 description 3
- 230000021523 carboxylation Effects 0.000 description 3
- 238000006473 carboxylation reaction Methods 0.000 description 3
- 150000001879 copper Chemical class 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 239000012954 diazonium Substances 0.000 description 3
- 150000001989 diazonium salts Chemical class 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- 229960001680 ibuprofen Drugs 0.000 description 3
- 230000006872 improvement Effects 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
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 230000020477 pH reduction Effects 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 235000019260 propionic acid Nutrition 0.000 description 3
- 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 3
- 230000009467 reduction Effects 0.000 description 3
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 2
- OXMIDRBAFOEOQT-UHFFFAOYSA-N 2,5-dimethyloxolane Chemical compound CC1CCC(C)O1 OXMIDRBAFOEOQT-UHFFFAOYSA-N 0.000 description 2
- UQRONKZLYKUEMO-UHFFFAOYSA-N 4-methyl-1-(2,4,6-trimethylphenyl)pent-4-en-2-one Chemical group CC(=C)CC(=O)Cc1c(C)cc(C)cc1C UQRONKZLYKUEMO-UHFFFAOYSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- 238000003747 Grignard reaction Methods 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 239000002260 anti-inflammatory agent Substances 0.000 description 2
- 239000012736 aqueous medium Substances 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 239000004305 biphenyl Substances 0.000 description 2
- 235000010290 biphenyl Nutrition 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
- 229910052799 carbon Inorganic materials 0.000 description 2
- 235000011089 carbon dioxide Nutrition 0.000 description 2
- RBHJBMIOOPYDBQ-UHFFFAOYSA-N carbon dioxide;propan-2-one Chemical compound O=C=O.CC(C)=O RBHJBMIOOPYDBQ-UHFFFAOYSA-N 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000006184 cosolvent Substances 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 2
- 229960005215 dichloroacetic acid Drugs 0.000 description 2
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 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 2
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 229910052742 iron Inorganic materials 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 2
- 229910052759 nickel Inorganic materials 0.000 description 2
- 150000002828 nitro derivatives Chemical class 0.000 description 2
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 2
- 235000015497 potassium bicarbonate Nutrition 0.000 description 2
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 2
- 239000011736 potassium bicarbonate Substances 0.000 description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 238000007086 side reaction Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- VOITXYVAKOUIBA-UHFFFAOYSA-N triethylaluminium Chemical compound CC[Al](CC)CC VOITXYVAKOUIBA-UHFFFAOYSA-N 0.000 description 2
- PZHIWRCQKBBTOW-UHFFFAOYSA-N 1-ethoxybutane Chemical compound CCCCOCC PZHIWRCQKBBTOW-UHFFFAOYSA-N 0.000 description 1
- YJLXEKFYZIBUPJ-UHFFFAOYSA-N 2,4-dibromo-6-fluoroaniline Chemical compound NC1=C(F)C=C(Br)C=C1Br YJLXEKFYZIBUPJ-UHFFFAOYSA-N 0.000 description 1
- CEPCPXLLFXPZGW-UHFFFAOYSA-N 2,4-difluoroaniline Chemical compound NC1=CC=C(F)C=C1F CEPCPXLLFXPZGW-UHFFFAOYSA-N 0.000 description 1
- ALZFPYUPNVLVQM-UHFFFAOYSA-N 2-bromo-6-fluoroaniline Chemical compound NC1=C(F)C=CC=C1Br ALZFPYUPNVLVQM-UHFFFAOYSA-N 0.000 description 1
- MONMFXREYOKQTI-UHFFFAOYSA-N 2-bromopropanoic acid Chemical compound CC(Br)C(O)=O MONMFXREYOKQTI-UHFFFAOYSA-N 0.000 description 1
- TWBPWBPGNQWFSJ-UHFFFAOYSA-N 2-phenylaniline Chemical group NC1=CC=CC=C1C1=CC=CC=C1 TWBPWBPGNQWFSJ-UHFFFAOYSA-N 0.000 description 1
- LBKMJZAKWQTTHC-UHFFFAOYSA-N 4-methyldioxolane Chemical compound CC1COOC1 LBKMJZAKWQTTHC-UHFFFAOYSA-N 0.000 description 1
- GMVPRGQOIOIIMI-DODZYUBVSA-N 7-[(1R,2R,3R)-3-hydroxy-2-[(3S)-3-hydroxyoct-1-enyl]-5-oxocyclopentyl]heptanoic acid Chemical compound CCCCC[C@H](O)C=C[C@H]1[C@H](O)CC(=O)[C@@H]1CCCCCCC(O)=O GMVPRGQOIOIIMI-DODZYUBVSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- 229910004039 HBF4 Inorganic materials 0.000 description 1
- 229910021576 Iron(III) bromide Inorganic materials 0.000 description 1
- 206010028400 Mutagenic effect Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical compound ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- PSLUFJFHTBIXMW-WYEYVKMPSA-N [(3r,4ar,5s,6s,6as,10s,10ar,10bs)-3-ethenyl-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-6-(2-pyridin-2-ylethylcarbamoyloxy)-5,6,6a,8,9,10-hexahydro-2h-benzo[f]chromen-5-yl] acetate Chemical compound O([C@@H]1[C@@H]([C@]2(O[C@](C)(CC(=O)[C@]2(O)[C@@]2(C)[C@@H](O)CCC(C)(C)[C@@H]21)C=C)C)OC(=O)C)C(=O)NCCC1=CC=CC=N1 PSLUFJFHTBIXMW-WYEYVKMPSA-N 0.000 description 1
- NQSUQAQPOPPGIN-UHFFFAOYSA-M [Br-].FC1=CC([Mg+])=CC=C1C1=CC=CC=C1 Chemical compound [Br-].FC1=CC([Mg+])=CC=C1C1=CC=CC=C1 NQSUQAQPOPPGIN-UHFFFAOYSA-M 0.000 description 1
- YUDRVAHLXDBKSR-UHFFFAOYSA-N [CH]1CCCCC1 Chemical compound [CH]1CCCCC1 YUDRVAHLXDBKSR-UHFFFAOYSA-N 0.000 description 1
- 239000006096 absorbing agent Substances 0.000 description 1
- 239000003377 acid catalyst Substances 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 229960004365 benzoic acid Drugs 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 description 1
- 229940106681 chloroacetic acid Drugs 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000002826 coolant Substances 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
- 125000002933 cyclohexyloxy group Chemical group C1(CCCCC1)O* 0.000 description 1
- 238000004042 decolorization Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- YNLAOSYQHBDIKW-UHFFFAOYSA-M diethylaluminium chloride Chemical compound CC[Al](Cl)CC YNLAOSYQHBDIKW-UHFFFAOYSA-M 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- NKDDWNXOKDWJAK-UHFFFAOYSA-N dimethoxymethane Chemical compound COCOC NKDDWNXOKDWJAK-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- ZLRROLLKQDRDPI-UHFFFAOYSA-L disodium;4,5-dihydroxybenzene-1,3-disulfonate;hydrate Chemical compound O.[Na+].[Na+].OC1=CC(S([O-])(=O)=O)=CC(S([O-])(=O)=O)=C1O ZLRROLLKQDRDPI-UHFFFAOYSA-L 0.000 description 1
- 229940082150 encore Drugs 0.000 description 1
- 230000007368 endocrine function Effects 0.000 description 1
- 239000004210 ether based solvent Substances 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- MGDOJPNDRJNJBK-UHFFFAOYSA-N ethylaluminum Chemical compound [Al].C[CH2] MGDOJPNDRJNJBK-UHFFFAOYSA-N 0.000 description 1
- 125000004705 ethylthio group Chemical group C(C)S* 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 238000001030 gas--liquid chromatography Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 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 1
- YPGCWEMNNLXISK-UHFFFAOYSA-N hydratropic acid Chemical compound OC(=O)C(C)C1=CC=CC=C1 YPGCWEMNNLXISK-UHFFFAOYSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 150000003949 imides Chemical class 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 150000002497 iodine compounds Chemical class 0.000 description 1
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- IBHRUOJKLLUBQG-UHFFFAOYSA-L magnesium;ethene;dibromide Chemical compound [Mg+2].[Br-].[Br-].C=C IBHRUOJKLLUBQG-UHFFFAOYSA-L 0.000 description 1
- UGVPKMAWLOMPRS-UHFFFAOYSA-M magnesium;propane;bromide Chemical compound [Mg+2].[Br-].CC[CH2-] UGVPKMAWLOMPRS-UHFFFAOYSA-M 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 231100000243 mutagenic effect Toxicity 0.000 description 1
- 230000003505 mutagenic effect Effects 0.000 description 1
- 125000004708 n-butylthio group Chemical group C(CCC)S* 0.000 description 1
- CSDTZUBPSYWZDX-UHFFFAOYSA-N n-pentyl nitrite Chemical compound CCCCCON=O CSDTZUBPSYWZDX-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 150000002816 nickel compounds Chemical class 0.000 description 1
- 150000002826 nitrites Chemical class 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- BKIMMITUMNQMOS-UHFFFAOYSA-N nonane Chemical compound CCCCCCCCC BKIMMITUMNQMOS-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- ANRQGKOBLBYXFM-UHFFFAOYSA-M phenylmagnesium bromide Chemical class Br[Mg]C1=CC=CC=C1 ANRQGKOBLBYXFM-UHFFFAOYSA-M 0.000 description 1
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 230000003637 steroidlike Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- 239000012485 toluene extract Substances 0.000 description 1
- 229940035339 tri-chlor Drugs 0.000 description 1
- FEONEKOZSGPOFN-UHFFFAOYSA-K tribromoiron Chemical compound Br[Fe](Br)Br FEONEKOZSGPOFN-UHFFFAOYSA-K 0.000 description 1
- 229960004319 trichloroacetic acid Drugs 0.000 description 1
- MCULRUJILOGHCJ-UHFFFAOYSA-N triisobutylaluminium Chemical compound CC(C)C[Al](CC(C)C)CC(C)C MCULRUJILOGHCJ-UHFFFAOYSA-N 0.000 description 1
- 238000013022 venting Methods 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F3/00—Compounds containing elements of Groups 2 or 12 of the Periodic Table
- C07F3/02—Magnesium compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/093—Preparation of halogenated hydrocarbons by replacement by halogens
- C07C17/10—Preparation of halogenated hydrocarbons by replacement by halogens of hydrogen atoms
- C07C17/12—Preparation of halogenated hydrocarbons by replacement by halogens of hydrogen atoms in the ring of aromatic compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/15—Preparation of carboxylic acids or their salts, halides or anhydrides by reaction of organic compounds with carbon dioxide, e.g. Kolbe-Schmitt synthesis
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pain & Pain Management (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Rheumatology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10506179A | 1979-12-19 | 1979-12-19 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH651288A5 true CH651288A5 (de) | 1985-09-13 |
Family
ID=22303841
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH9120/80A CH651288A5 (de) | 1979-12-19 | 1980-12-10 | Verfahren zur herstellung von hydratropsaeurederivaten. |
Country Status (7)
| Country | Link |
|---|---|
| JP (1) | JPS5697246A (fr) |
| CH (1) | CH651288A5 (fr) |
| DE (1) | DE3046523A1 (fr) |
| FR (1) | FR2473507B1 (fr) |
| GB (1) | GB2065656B (fr) |
| IT (1) | IT1128706B (fr) |
| NL (1) | NL8006488A (fr) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4910337A (en) * | 1989-01-27 | 1990-03-20 | Mine Safety Appliances Company | Process for the preparation of α-arylalkanoic acids |
| IE913655A1 (en) * | 1990-11-06 | 1992-05-22 | Zeneca Ltd | Synergistic agents |
| AU2008345573B2 (en) | 2007-12-20 | 2013-12-19 | Envivo Pharmaceuticals, Inc. | Tetrasubstituted benzenes |
| CN101973869B (zh) * | 2010-11-02 | 2013-05-29 | 中国科学技术大学 | 一种合成氟比洛芬的方法 |
| CN107936045B (zh) * | 2017-12-01 | 2019-10-18 | 北京茗泽中和药物研究有限公司 | 一种高纯度氟比洛芬已知杂质的制备方法 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2452154A (en) * | 1942-04-15 | 1948-10-26 | Colgate Palmolive Peet Co | Bromination |
| US3359364A (en) * | 1963-04-01 | 1967-12-19 | Sony Corp | Recording and/or reproducing system |
| GB1091403A (en) * | 1964-01-24 | 1967-11-15 | Boots Pure Drug Co Ltd | Therapeutically active phenylalkane derivatives |
| US3992459A (en) * | 1975-05-01 | 1976-11-16 | Merck & Co., Inc. | Preparation of biphenyl compounds |
| US3987057A (en) * | 1975-01-30 | 1976-10-19 | E. I. Du Pont De Nemours And Company | Herbicidal 2-(substituted aryl)-3a,4,5,6,7,7a-hexahydro-1h-isoindole-1,3(2h)-diones |
-
1980
- 1980-11-28 NL NL8006488A patent/NL8006488A/nl not_active Application Discontinuation
- 1980-12-10 CH CH9120/80A patent/CH651288A5/de not_active IP Right Cessation
- 1980-12-10 DE DE19803046523 patent/DE3046523A1/de not_active Ceased
- 1980-12-16 GB GB8040295A patent/GB2065656B/en not_active Expired
- 1980-12-18 FR FR8026940A patent/FR2473507B1/fr not_active Expired
- 1980-12-18 IT IT50410/80A patent/IT1128706B/it active
- 1980-12-19 JP JP17915080A patent/JPS5697246A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| DE3046523A1 (de) | 1981-08-27 |
| IT1128706B (it) | 1986-06-04 |
| JPS5697246A (en) | 1981-08-05 |
| FR2473507A1 (fr) | 1981-07-17 |
| IT8050410A0 (it) | 1980-12-18 |
| GB2065656B (en) | 1983-06-22 |
| GB2065656A (en) | 1981-07-01 |
| FR2473507B1 (fr) | 1985-09-06 |
| NL8006488A (nl) | 1981-07-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE3046512A1 (de) | Verfahren zur kupplung von anilin- und phenyl-verbindungen | |
| DE2439294A1 (de) | Neue phenyl-alkenole und alkanole und verfahren zu deren herstellung | |
| DE2542612C2 (fr) | ||
| CH651288A5 (de) | Verfahren zur herstellung von hydratropsaeurederivaten. | |
| EP0034741A2 (fr) | Procédé pour la préparation d'un bromofluorobenzène substitué et de 3-bromo-4-fluorobenzonitrile | |
| DE3214828A1 (de) | Phosphorverbindungen | |
| DE2708190A1 (de) | M-brom-benzotrifluoride | |
| DE3046522A1 (de) | Halogenierung von 2-fluoranilin | |
| DE19850788A1 (de) | Verfahren zur Herstellung von Trifluorbenzoesäuren | |
| EP0114359A1 (fr) | Procédé pour la préparation de composés carbocycliques ou hétérocycliques substitués par un groupe perfluoroalkyle | |
| DE69604327T2 (de) | Herstellung von polyalkylierten Cyclopentadienen aus Isobornylcarboxylaten | |
| DE2932198A1 (de) | Verfahren zur herstellung von o-(2,6-dichloranilino)-phenylessigsaeure und neue zwischenprodukte zur durchfuehrung des verfahrens | |
| EP1223158A1 (fr) | Procédé de préparation d'acides biphényl carboxyliques substitués par un groupe trifluoromethyl et nouveaux nitriles de biphényl substitués par un groupe trifluoro- ou trichloro- methyl | |
| DE69903498T2 (de) | Verfahren zur Herstellung von 13-cis-Retinsäure | |
| AT203485B (de) | Verfahren zur Herstellung von neuen Dinitrophenylmethacrylaten | |
| DE2505446A1 (de) | Neue organische verbindungen und verfahren zu deren herstellung | |
| DE3216851A1 (de) | Verfahren zur herstellung von substituierten biphenylverbindungen | |
| AT247847B (de) | Verfahren zur Herstellung von neuen 5-(3'-Aminopropyliden)-5H-dibenzo [a, d] cycloheptenen bzw. den 10, 11-Dihydroderivaten derselben | |
| EP0048370A1 (fr) | Procédé de préparation de dérivés des acides trans-3-(Z-2-chloro-2-aryl-vinyl)-2,2-diméthyl-cyclopropane-carboxyliques, produits intermédiaires à cet effet, procédé de préparation de ces produits intermédiaires et leur utilisation dans des pesticides | |
| DE10361426A1 (de) | Pyrazolylaryllalkine | |
| EP0529444B1 (fr) | Acides 2-arylpropéniques et leur utilisation dans la préparation de 5-kétoprofen | |
| DE4414841A1 (de) | Brom enthaltende aromatische Verbindungen, Verfahren zu ihrer Herstellung und ihre Verwendung als Zwischenprodukte bei der Synthese von Wirkstoffen | |
| AT211806B (de) | Verfahren zur Herstellung von ungesättigten aliphatischen Verbindungen | |
| DE2224791A1 (de) | Verfahren zur Herstellung von Alkinylarylverbindungen | |
| DE2341044A1 (de) | Neue substituierte pivaloylphenylderivate und verfahren zu deren herstellung |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PL | Patent ceased |