JPS6113473B2 - - Google Patents
Info
- Publication number
- JPS6113473B2 JPS6113473B2 JP52131639A JP13163977A JPS6113473B2 JP S6113473 B2 JPS6113473 B2 JP S6113473B2 JP 52131639 A JP52131639 A JP 52131639A JP 13163977 A JP13163977 A JP 13163977A JP S6113473 B2 JPS6113473 B2 JP S6113473B2
- Authority
- JP
- Japan
- Prior art keywords
- methyl
- phenyl
- chloro
- benzodioxin
- hydrogen atom
- 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.)
- Expired
Links
- 150000001875 compounds Chemical class 0.000 claims description 164
- 239000000203 mixture Substances 0.000 claims description 108
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 82
- -1 (2,2-dimethyl-1,3 -dioxolan-4-yl) methyl group Chemical group 0.000 claims description 56
- 239000000460 chlorine Substances 0.000 claims description 51
- 239000002253 acid Substances 0.000 claims description 50
- 239000001257 hydrogen Substances 0.000 claims description 39
- 229910052739 hydrogen Inorganic materials 0.000 claims description 39
- 125000004432 carbon atom Chemical group C* 0.000 claims description 36
- 125000000217 alkyl group Chemical group 0.000 claims description 34
- 150000003839 salts Chemical class 0.000 claims description 33
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 31
- 229910052783 alkali metal Inorganic materials 0.000 claims description 22
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 22
- UMBAPIWARGTVLV-UHFFFAOYSA-N 6-chloro-4-methyl-4-phenyl-1,3-benzodioxine-2-carboxylic acid Chemical compound O1C(C(O)=O)OC2=CC=C(Cl)C=C2C1(C)C1=CC=CC=C1 UMBAPIWARGTVLV-UHFFFAOYSA-N 0.000 claims description 21
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
- 150000001340 alkali metals Chemical class 0.000 claims description 17
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 17
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 16
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 16
- 150000001342 alkaline earth metals Chemical class 0.000 claims description 16
- 229910052801 chlorine Inorganic materials 0.000 claims description 16
- 229910052782 aluminium Inorganic materials 0.000 claims description 15
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 15
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 15
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 13
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
- 238000004519 manufacturing process Methods 0.000 claims description 12
- 150000007513 acids Chemical class 0.000 claims description 10
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 9
- 239000003795 chemical substances by application Substances 0.000 claims description 9
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 8
- 125000005843 halogen group Chemical group 0.000 claims description 8
- BKOZCSAXFAMFGZ-UHFFFAOYSA-N 6-chloro-2,4-dimethyl-4-phenyl-1,3-benzodioxine-2-carboxylic acid Chemical compound O1C(C)(C(O)=O)OC2=CC=C(Cl)C=C2C1(C)C1=CC=CC=C1 BKOZCSAXFAMFGZ-UHFFFAOYSA-N 0.000 claims description 7
- 239000003054 catalyst Substances 0.000 claims description 6
- 239000004305 biphenyl Substances 0.000 claims description 5
- 150000002632 lipids Chemical class 0.000 claims description 5
- JWKJDAVEKUGNOJ-UHFFFAOYSA-N 4-methyl-4-phenyl-1,3-benzodioxine-2-carboxylic acid Chemical compound O1C(C(O)=O)OC2=CC=CC=C2C1(C)C1=CC=CC=C1 JWKJDAVEKUGNOJ-UHFFFAOYSA-N 0.000 claims description 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 4
- 239000008280 blood Substances 0.000 claims description 4
- 210000004369 blood Anatomy 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- BYSUSVMYOUNXLV-UHFFFAOYSA-N ethyl 6-chloro-4-methyl-4-phenyl-1,3-benzodioxine-2-carboxylate Chemical compound O1C(C(=O)OCC)OC2=CC=C(Cl)C=C2C1(C)C1=CC=CC=C1 BYSUSVMYOUNXLV-UHFFFAOYSA-N 0.000 claims description 4
- 229910052740 iodine Inorganic materials 0.000 claims description 4
- 150000003053 piperidines Chemical class 0.000 claims description 4
- UUFBBGQWKAVCMF-UHFFFAOYSA-N 6-chloro-4-(3-chlorophenyl)-4-methyl-1,3-benzodioxine-2-carboxylic acid Chemical compound O1C(C(O)=O)OC2=CC=C(Cl)C=C2C1(C)C1=CC=CC(Cl)=C1 UUFBBGQWKAVCMF-UHFFFAOYSA-N 0.000 claims description 3
- MITWXOAINMITLF-UHFFFAOYSA-N 6-chloro-4-phenyl-4h-1,3-benzodioxine-2-carboxylic acid Chemical compound C12=CC(Cl)=CC=C2OC(C(=O)O)OC1C1=CC=CC=C1 MITWXOAINMITLF-UHFFFAOYSA-N 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 3
- HQPLKMWKZCOKOM-UHFFFAOYSA-N methyl 6-chloro-4-methyl-4-phenyl-1,3-benzodioxine-2-carboxylate Chemical class O1C(C(=O)OC)OC2=CC=C(Cl)C=C2C1(C)C1=CC=CC=C1 HQPLKMWKZCOKOM-UHFFFAOYSA-N 0.000 claims description 2
- YZCKVEUIGOORGS-IGMARMGPSA-N Protium Chemical compound [1H] YZCKVEUIGOORGS-IGMARMGPSA-N 0.000 claims 2
- NIBAXWVNEGNVMN-UHFFFAOYSA-N 4-tert-butyl-6-chloro-4-phenyl-1,3-benzodioxine-2-carboxylic acid Chemical compound O1C(C(O)=O)OC2=CC=C(Cl)C=C2C1(C(C)(C)C)C1=CC=CC=C1 NIBAXWVNEGNVMN-UHFFFAOYSA-N 0.000 claims 1
- 150000001339 alkali metal compounds Chemical class 0.000 claims 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 claims 1
- 238000002955 isolation Methods 0.000 claims 1
- UWVWENVKWBPTSG-UHFFFAOYSA-M sodium;6-chloro-4-methyl-4-phenyl-1,3-benzodioxine-2-carboxylate Chemical compound [Na+].O1C(C([O-])=O)OC2=CC=C(Cl)C=C2C1(C)C1=CC=CC=C1 UWVWENVKWBPTSG-UHFFFAOYSA-M 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 203
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 102
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 102
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 86
- 239000000243 solution Substances 0.000 description 75
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 73
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 60
- 238000003756 stirring Methods 0.000 description 53
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 52
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 48
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 45
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 42
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 40
- 238000004458 analytical method Methods 0.000 description 40
- 238000004364 calculation method Methods 0.000 description 39
- 238000005259 measurement Methods 0.000 description 39
- 239000008346 aqueous phase Substances 0.000 description 36
- 125000003118 aryl group Chemical group 0.000 description 36
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 36
- 239000000284 extract Substances 0.000 description 35
- 239000012071 phase Substances 0.000 description 33
- 239000002904 solvent Substances 0.000 description 32
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 30
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 26
- 235000019341 magnesium sulphate Nutrition 0.000 description 26
- 239000012074 organic phase Substances 0.000 description 26
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 24
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 24
- 238000010992 reflux Methods 0.000 description 24
- 239000012043 crude product Substances 0.000 description 23
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 21
- 238000000034 method Methods 0.000 description 20
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 17
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 16
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
- 239000007788 liquid Substances 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 239000000047 product Substances 0.000 description 14
- GKIRPKYJQBWNGO-OCEACIFDSA-N clomifene Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 GKIRPKYJQBWNGO-OCEACIFDSA-N 0.000 description 13
- 239000002244 precipitate Substances 0.000 description 13
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
- JXTHNDFMNIQAHM-UHFFFAOYSA-N dichloroacetic acid Chemical compound OC(=O)C(Cl)Cl JXTHNDFMNIQAHM-UHFFFAOYSA-N 0.000 description 12
- 238000001035 drying Methods 0.000 description 12
- 239000000725 suspension Substances 0.000 description 12
- 239000013078 crystal Substances 0.000 description 11
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 10
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 9
- 239000011347 resin Substances 0.000 description 9
- 229920005989 resin Polymers 0.000 description 9
- 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 8
- 239000007864 aqueous solution Substances 0.000 description 8
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 8
- 239000003208 petroleum Substances 0.000 description 8
- 229910052708 sodium Inorganic materials 0.000 description 8
- 239000011734 sodium Substances 0.000 description 8
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 8
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 7
- 229910020366 ClO 4 Inorganic materials 0.000 description 7
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 7
- 239000006286 aqueous extract Substances 0.000 description 7
- 239000001110 calcium chloride Substances 0.000 description 7
- 229910001628 calcium chloride Inorganic materials 0.000 description 7
- 239000003960 organic solvent Substances 0.000 description 7
- 239000000377 silicon dioxide Substances 0.000 description 7
- 239000012312 sodium hydride Substances 0.000 description 7
- 229910000104 sodium hydride Inorganic materials 0.000 description 7
- 238000005406 washing Methods 0.000 description 7
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
- 229960005215 dichloroacetic acid Drugs 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 230000003287 optical effect Effects 0.000 description 6
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 5
- 239000002671 adjuvant Substances 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 229910052799 carbon Inorganic materials 0.000 description 5
- 235000012000 cholesterol Nutrition 0.000 description 5
- 238000001704 evaporation Methods 0.000 description 5
- 239000011777 magnesium Substances 0.000 description 5
- 239000012452 mother liquor Substances 0.000 description 5
- KDGSZJXXQWMOKP-UHFFFAOYSA-M potassium;2,2-dichloroacetate Chemical compound [K+].[O-]C(=O)C(Cl)Cl KDGSZJXXQWMOKP-UHFFFAOYSA-M 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 description 5
- 239000000454 talc Substances 0.000 description 5
- 229910052623 talc Inorganic materials 0.000 description 5
- RPBJDGUXTSCXJX-UHFFFAOYSA-N 4-chloro-2-(1-hydroxy-1-phenylethyl)phenol Chemical compound C=1C(Cl)=CC=C(O)C=1C(O)(C)C1=CC=CC=C1 RPBJDGUXTSCXJX-UHFFFAOYSA-N 0.000 description 4
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 4
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 4
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 4
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 4
- 150000001721 carbon Chemical group 0.000 description 4
- 239000012141 concentrate Substances 0.000 description 4
- 238000007796 conventional method Methods 0.000 description 4
- 238000005520 cutting process Methods 0.000 description 4
- YSSSPARMOAYJTE-UHFFFAOYSA-N dibenzo-18-crown-6 Chemical compound O1CCOCCOC2=CC=CC=C2OCCOCCOC2=CC=CC=C21 YSSSPARMOAYJTE-UHFFFAOYSA-N 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 239000012259 ether extract Substances 0.000 description 4
- 239000005457 ice water Substances 0.000 description 4
- 229910052749 magnesium Inorganic materials 0.000 description 4
- 229910052700 potassium Inorganic materials 0.000 description 4
- 239000011591 potassium Substances 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 150000003626 triacylglycerols Chemical class 0.000 description 4
- NAMYKGVDVNBCFQ-UHFFFAOYSA-N 2-bromopropane Chemical compound CC(C)Br NAMYKGVDVNBCFQ-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 235000019270 ammonium chloride Nutrition 0.000 description 3
- 239000012300 argon atmosphere Substances 0.000 description 3
- 239000012752 auxiliary agent Substances 0.000 description 3
- 229960004217 benzyl alcohol Drugs 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 125000001153 fluoro group Chemical group F* 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000007903 gelatin capsule Substances 0.000 description 3
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- FFLRUFAKDDZPJP-UHFFFAOYSA-N methyl 1,4-benzodioxine-3-carboxylate Chemical compound C1=CC=C2OC(C(=O)OC)=COC2=C1 FFLRUFAKDDZPJP-UHFFFAOYSA-N 0.000 description 3
- 229910052763 palladium Inorganic materials 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- FORQJPGZFJPPMV-UHFFFAOYSA-N (4-chlorophenyl) 3-chlorobenzoate Chemical compound C1=CC(Cl)=CC=C1OC(=O)C1=CC=CC(Cl)=C1 FORQJPGZFJPPMV-UHFFFAOYSA-N 0.000 description 2
- LRVSNASUZRUMJW-UHFFFAOYSA-N (5-chloro-2-hydroxyphenyl)-(3-chlorophenyl)methanone Chemical compound OC1=CC=C(Cl)C=C1C(=O)C1=CC=CC(Cl)=C1 LRVSNASUZRUMJW-UHFFFAOYSA-N 0.000 description 2
- OMWSZDODENFLSV-UHFFFAOYSA-N (5-chloro-2-hydroxyphenyl)-phenylmethanone Chemical compound OC1=CC=C(Cl)C=C1C(=O)C1=CC=CC=C1 OMWSZDODENFLSV-UHFFFAOYSA-N 0.000 description 2
- XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 2
- OCYJXSUPZMNXEN-UHFFFAOYSA-N 2-amino-1-(4-nitrophenyl)propane-1,3-diol Chemical class OCC(N)C(O)C1=CC=C([N+]([O-])=O)C=C1 OCYJXSUPZMNXEN-UHFFFAOYSA-N 0.000 description 2
- SRYHBJWIJKVZJK-UHFFFAOYSA-N 6-chloro-4-(4-chlorophenyl)-4-methyl-1,3-benzodioxine-2-carboxylic acid Chemical compound O1C(C(O)=O)OC2=CC=C(Cl)C=C2C1(C)C1=CC=C(Cl)C=C1 SRYHBJWIJKVZJK-UHFFFAOYSA-N 0.000 description 2
- RXUBHAYSLKWGQM-UHFFFAOYSA-N 6-fluoro-4-methyl-4-phenyl-1,3-benzodioxine-2-carboxylic acid Chemical compound O1C(C(O)=O)OC2=CC=C(F)C=C2C1(C)C1=CC=CC=C1 RXUBHAYSLKWGQM-UHFFFAOYSA-N 0.000 description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
- 229910002012 Aerosil® Inorganic materials 0.000 description 2
- 229910015900 BF3 Inorganic materials 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- NOTFZGFABLVTIG-UHFFFAOYSA-N Cyclohexylethyl acetate Chemical compound CC(=O)OCCC1CCCCC1 NOTFZGFABLVTIG-UHFFFAOYSA-N 0.000 description 2
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 231100000111 LD50 Toxicity 0.000 description 2
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- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- PWNLNTSBWIDQAA-UHFFFAOYSA-M potassium;2,2-dibromoacetate Chemical compound [K+].[O-]C(=O)C(Br)Br PWNLNTSBWIDQAA-UHFFFAOYSA-M 0.000 description 1
- 239000004540 pour-on Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- KCXFHTAICRTXLI-UHFFFAOYSA-N propane-1-sulfonic acid Chemical compound CCCS(O)(=O)=O KCXFHTAICRTXLI-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000010956 selective crystallization Methods 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- PDEFQWNXOUGDJR-UHFFFAOYSA-M sodium;2,2-dichloropropanoate Chemical compound [Na+].CC(Cl)(Cl)C([O-])=O PDEFQWNXOUGDJR-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- RNVYQYLELCKWAN-UHFFFAOYSA-N solketal Chemical compound CC1(C)OCC(CO)O1 RNVYQYLELCKWAN-UHFFFAOYSA-N 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000005809 transesterification reaction Methods 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D319/04—1,3-Dioxanes; Hydrogenated 1,3-dioxanes
- C07D319/08—1,3-Dioxanes; Hydrogenated 1,3-dioxanes condensed with carbocyclic rings or ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/51—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition
- C07C45/54—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition of compounds containing doubly bound oxygen atoms, e.g. esters
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR7633409A FR2369838A1 (fr) | 1976-11-05 | 1976-11-05 | Nouveaux derives de (1-3) benzodioxine, un procede pour leur preparation et leur application comme medicaments |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5359676A JPS5359676A (en) | 1978-05-29 |
| JPS6113473B2 true JPS6113473B2 (OSRAM) | 1986-04-14 |
Family
ID=9179584
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP13163977A Granted JPS5359676A (en) | 1976-11-05 | 1977-11-04 | Production of novel 1*33 benzooxine derivatives and pharmaceutical composition |
Country Status (17)
| Country | Link |
|---|---|
| JP (1) | JPS5359676A (OSRAM) |
| AT (1) | AT360986B (OSRAM) |
| AU (1) | AU515307B2 (OSRAM) |
| BE (1) | BE860500A (OSRAM) |
| CH (1) | CH625517A5 (OSRAM) |
| DE (1) | DE2749279C2 (OSRAM) |
| DK (1) | DK152429C (OSRAM) |
| ES (1) | ES463842A1 (OSRAM) |
| FR (1) | FR2369838A1 (OSRAM) |
| GB (1) | GB1590169A (OSRAM) |
| HU (1) | HU179057B (OSRAM) |
| IE (1) | IE46172B1 (OSRAM) |
| IL (1) | IL53232A (OSRAM) |
| LU (1) | LU78456A1 (OSRAM) |
| NL (1) | NL7712172A (OSRAM) |
| SE (1) | SE436879B (OSRAM) |
| ZA (1) | ZA776529B (OSRAM) |
-
1976
- 1976-11-05 FR FR7633409A patent/FR2369838A1/fr active Granted
-
1977
- 1977-10-17 SE SE7711669A patent/SE436879B/xx not_active IP Right Cessation
- 1977-10-26 IL IL53232A patent/IL53232A/xx unknown
- 1977-11-02 ZA ZA00776529A patent/ZA776529B/xx unknown
- 1977-11-03 HU HU77RO948A patent/HU179057B/hu not_active IP Right Cessation
- 1977-11-03 DE DE2749279A patent/DE2749279C2/de not_active Expired
- 1977-11-04 JP JP13163977A patent/JPS5359676A/ja active Granted
- 1977-11-04 AU AU30329/77A patent/AU515307B2/en not_active Expired
- 1977-11-04 CH CH1345677A patent/CH625517A5/fr not_active IP Right Cessation
- 1977-11-04 BE BE182360A patent/BE860500A/xx not_active IP Right Cessation
- 1977-11-04 LU LU78456A patent/LU78456A1/xx unknown
- 1977-11-04 ES ES463842A patent/ES463842A1/es not_active Expired
- 1977-11-04 NL NL7712172A patent/NL7712172A/xx not_active Application Discontinuation
- 1977-11-04 DK DK490477A patent/DK152429C/da not_active IP Right Cessation
- 1977-11-07 GB GB46192/77A patent/GB1590169A/en not_active Expired
- 1977-11-07 AT AT793377A patent/AT360986B/de not_active IP Right Cessation
- 1977-11-07 IE IE2268/77A patent/IE46172B1/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| DK152429B (da) | 1988-02-29 |
| IE46172B1 (en) | 1983-03-23 |
| IL53232A (en) | 1982-05-31 |
| BE860500A (fr) | 1978-05-05 |
| ES463842A1 (es) | 1978-06-16 |
| SE7711669L (sv) | 1978-05-06 |
| AU3032977A (en) | 1979-06-14 |
| HU179057B (en) | 1982-08-28 |
| GB1590169A (en) | 1981-05-28 |
| JPS5359676A (en) | 1978-05-29 |
| ZA776529B (en) | 1978-12-27 |
| FR2369838A1 (fr) | 1978-06-02 |
| DE2749279A1 (de) | 1978-05-11 |
| AU515307B2 (en) | 1981-03-26 |
| LU78456A1 (OSRAM) | 1978-07-14 |
| IL53232A0 (en) | 1977-12-30 |
| ATA793377A (de) | 1980-07-15 |
| DK152429C (da) | 1988-07-25 |
| AT360986B (de) | 1981-02-10 |
| SE436879B (sv) | 1985-01-28 |
| FR2369838B1 (OSRAM) | 1979-06-29 |
| IE46172L (en) | 1978-05-05 |
| CH625517A5 (en) | 1981-09-30 |
| DK490477A (da) | 1978-05-06 |
| DE2749279C2 (de) | 1985-11-14 |
| NL7712172A (nl) | 1978-05-09 |
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