BE482452A - - Google Patents

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Publication number

BE482452A

BE482452A BE482452DA BE482452A BE 482452 A BE482452 A BE 482452A BE 482452D A BE482452D A BE 482452DA BE 482452 A BE482452 A BE 482452A

Authority

BE

Belgium

Prior art keywords

parts

water

oxy

solution

ether

Prior art date

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• 238000000034 method Methods 0.000 claims description 19
• 239000002253 acid Substances 0.000 claims description 17
• 150000001875 compounds Chemical class 0.000 claims description 17
• 150000002148 esters Chemical class 0.000 claims description 16
• 238000007254 oxidation reaction Methods 0.000 claims description 15
• 239000003795 chemical substances by application Substances 0.000 claims description 14
• 230000003647 oxidation Effects 0.000 claims description 14
• 230000008569 process Effects 0.000 claims description 14
• 125000000468 ketone group Chemical group 0.000 claims description 7
• 238000006243 chemical reaction Methods 0.000 claims description 6
• 150000003839 salts Chemical class 0.000 claims description 4
• 125000001424 substituent group Chemical group 0.000 claims description 4
• 230000015572 biosynthetic process Effects 0.000 claims description 3
• 238000006731 degradation reaction Methods 0.000 claims description 2
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
• 229910052799 carbon Inorganic materials 0.000 claims 1
• 230000015556 catabolic process Effects 0.000 claims 1
• 238000002560 therapeutic procedure Methods 0.000 claims 1
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 86
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 59
• 239000000243 solution Substances 0.000 description 57
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 45
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 32
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 20
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 20
• 239000000203 mixture Substances 0.000 description 20
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
• VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 14
• 239000000155 melt Substances 0.000 description 12
• VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 10
• 229910000029 sodium carbonate Inorganic materials 0.000 description 10
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
• PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 9
• 230000009471 action Effects 0.000 description 8
• SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 8
• 238000010992 reflux Methods 0.000 description 8
• 239000000725 suspension Substances 0.000 description 8
• YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 7
• KRVSOGSZCMJSLX-UHFFFAOYSA-L chromic acid Substances O[Cr](O)(=O)=O KRVSOGSZCMJSLX-UHFFFAOYSA-L 0.000 description 7
• 229940117975 chromium trioxide Drugs 0.000 description 7
• WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 7
• GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 0.000 description 7
• AWJWCTOOIBYHON-UHFFFAOYSA-N furo[3,4-b]pyrazine-5,7-dione Chemical compound C1=CN=C2C(=O)OC(=O)C2=N1 AWJWCTOOIBYHON-UHFFFAOYSA-N 0.000 description 7
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
• 150000004702 methyl esters Chemical class 0.000 description 6
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 5
• 150000007513 acids Chemical class 0.000 description 5
• 239000007900 aqueous suspension Substances 0.000 description 5
• 229910000019 calcium carbonate Inorganic materials 0.000 description 5
• 239000000047 product Substances 0.000 description 5
• DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 4
• 125000004432 carbon atom Chemical group C* 0.000 description 4
• 230000003301 hydrolyzing effect Effects 0.000 description 4
• 235000011056 potassium acetate Nutrition 0.000 description 4
• 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 4
• 230000009466 transformation Effects 0.000 description 4
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
• -1 benzyl alcohol, tetra-acylated glucose Chemical class 0.000 description 3
• 150000001735 carboxylic acids Chemical class 0.000 description 3
• 125000005843 halogen group Chemical group 0.000 description 3
• 238000002844 melting Methods 0.000 description 3
• 230000008018 melting Effects 0.000 description 3
• 229910052751 metal Inorganic materials 0.000 description 3
• 239000002184 metal Substances 0.000 description 3
• 150000004707 phenolate Chemical class 0.000 description 3
• 238000001953 recrystallisation Methods 0.000 description 3
• 150000003460 sulfonic acids Chemical class 0.000 description 3
• UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
• MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
• OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical class CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• 150000001242 acetic acid derivatives Chemical class 0.000 description 2
• 150000001298 alcohols Chemical class 0.000 description 2
• 239000007864 aqueous solution Substances 0.000 description 2
• 239000003125 aqueous solvent Substances 0.000 description 2
• 150000001558 benzoic acid derivatives Chemical class 0.000 description 2
• 238000009835 boiling Methods 0.000 description 2
• 239000001110 calcium chloride Substances 0.000 description 2
• 229910001628 calcium chloride Inorganic materials 0.000 description 2
• 150000004649 carbonic acid derivatives Chemical class 0.000 description 2
• 239000003153 chemical reaction reagent Substances 0.000 description 2
• 238000001816 cooling Methods 0.000 description 2
• 239000003085 diluting agent Substances 0.000 description 2
• 150000002170 ethers Chemical group 0.000 description 2
• 238000010438 heat treatment Methods 0.000 description 2
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
• 239000003960 organic solvent Substances 0.000 description 2
• 239000007800 oxidant agent Substances 0.000 description 2
• 230000001590 oxidative effect Effects 0.000 description 2
• 150000002989 phenols Chemical class 0.000 description 2
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
• 238000002360 preparation method Methods 0.000 description 2
• 239000011541 reaction mixture Substances 0.000 description 2
• 229920006395 saturated elastomer Polymers 0.000 description 2
• 230000007017 scission Effects 0.000 description 2
• 150000003512 tertiary amines Chemical class 0.000 description 2
• PBXJGQQGODZSQR-WQBJWTDHSA-N (5s,8r,9s,10s,13s,14s,17s)-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthrene-17-carboxylic acid Chemical compound C1CCC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)C(O)=O)[C@@H]4[C@@H]3CC[C@@H]21 PBXJGQQGODZSQR-WQBJWTDHSA-N 0.000 description 1
• POPBYCBXVLHSKO-UHFFFAOYSA-N 9,10-dioxoanthracene-1-carboxylic acid Chemical class O=C1C2=CC=CC=C2C(=O)C2=C1C=CC=C2C(=O)O POPBYCBXVLHSKO-UHFFFAOYSA-N 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
• 239000004593 Epoxy Substances 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
• OPFJDXRVMFKJJO-ZHHKINOHSA-N N-{[3-(2-benzamido-4-methyl-1,3-thiazol-5-yl)-pyrazol-5-yl]carbonyl}-G-dR-G-dD-dD-dD-NH2 Chemical compound S1C(C=2NN=C(C=2)C(=O)NCC(=O)N[C@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(N)=O)=C(C)N=C1NC(=O)C1=CC=CC=C1 OPFJDXRVMFKJJO-ZHHKINOHSA-N 0.000 description 1
• BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
• CJOGFYZQRHJZRG-VDIPWFLFSA-N [4-[(8R,9S,10S,13S,14S)-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl]-1,1-diphenylpenta-1,3-dien-2-yl] acetate Chemical compound C(C)(=O)OC(=C(C1=CC=CC=C1)C1=CC=CC=C1)C=C(C)C1=CC[C@H]2[C@@H]3CCC4CCCC[C@]4(C)[C@H]3CC[C@]12C CJOGFYZQRHJZRG-VDIPWFLFSA-N 0.000 description 1
• XXFXTBNFFMQVKJ-UHFFFAOYSA-N [diphenyl(trityloxy)methyl]benzene Chemical class C=1C=CC=CC=1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)OC(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 XXFXTBNFFMQVKJ-UHFFFAOYSA-N 0.000 description 1
• WDJHALXBUFZDSR-UHFFFAOYSA-N acetoacetic acid Chemical compound CC(=O)CC(O)=O WDJHALXBUFZDSR-UHFFFAOYSA-N 0.000 description 1
• 150000008065 acid anhydrides Chemical class 0.000 description 1
• 239000012445 acidic reagent Substances 0.000 description 1
• 125000002252 acyl group Chemical group 0.000 description 1
• 125000004423 acyloxy group Chemical group 0.000 description 1
• 239000003470 adrenal cortex hormone Substances 0.000 description 1
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 150000001340 alkali metals Chemical class 0.000 description 1
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
• 150000001342 alkaline earth metals Chemical class 0.000 description 1
• 125000003545 alkoxy group Chemical group 0.000 description 1
• 125000005910 alkyl carbonate group Chemical group 0.000 description 1
• 125000000217 alkyl group Chemical group 0.000 description 1
• 125000003118 aryl group Chemical group 0.000 description 1
• 239000003613 bile acid Substances 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 238000010504 bond cleavage reaction Methods 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
• 150000001728 carbonyl compounds Chemical class 0.000 description 1
• 238000004587 chromatography analysis Methods 0.000 description 1
• JOPOVCBBYLSVDA-UHFFFAOYSA-N chromium(6+) Chemical compound [Cr+6] JOPOVCBBYLSVDA-UHFFFAOYSA-N 0.000 description 1
• 238000003776 cleavage reaction Methods 0.000 description 1
• 229940126086 compound 21 Drugs 0.000 description 1
• 239000012141 concentrate Substances 0.000 description 1
• 239000013078 crystal Substances 0.000 description 1
• 238000002425 crystallisation Methods 0.000 description 1
• 230000008025 crystallization Effects 0.000 description 1
• 230000000593 degrading effect Effects 0.000 description 1
• 150000001993 dienes Chemical group 0.000 description 1
• 239000003814 drug Substances 0.000 description 1
• 230000032050 esterification Effects 0.000 description 1
• 238000005886 esterification reaction Methods 0.000 description 1
• 238000006266 etherification reaction Methods 0.000 description 1
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• 229930182478 glucoside Natural products 0.000 description 1
• 150000008131 glucosides Chemical class 0.000 description 1
• 150000002334 glycols Chemical class 0.000 description 1
• 150000004820 halides Chemical group 0.000 description 1
• 229910052736 halogen Inorganic materials 0.000 description 1
• 150000002367 halogens Chemical class 0.000 description 1
• 239000005556 hormone Substances 0.000 description 1
• 229940088597 hormone Drugs 0.000 description 1
• 230000007062 hydrolysis Effects 0.000 description 1
• 238000006460 hydrolysis reaction Methods 0.000 description 1
• 150000004679 hydroxides Chemical class 0.000 description 1
• 239000012442 inert solvent Substances 0.000 description 1
• 239000000543 intermediate Substances 0.000 description 1
• 150000002576 ketones Chemical class 0.000 description 1
• 150000002597 lactoses Chemical class 0.000 description 1
• 229910000000 metal hydroxide Inorganic materials 0.000 description 1
• 150000004692 metal hydroxides Chemical class 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
• 230000011987 methylation Effects 0.000 description 1
• 238000007069 methylation reaction Methods 0.000 description 1
• 239000012285 osmium tetroxide Substances 0.000 description 1
• 229910000489 osmium tetroxide Inorganic materials 0.000 description 1
• 238000010525 oxidative degradation reaction Methods 0.000 description 1
• 238000006385 ozonation reaction Methods 0.000 description 1
• 150000002978 peroxides Chemical class 0.000 description 1
• 239000003208 petroleum Substances 0.000 description 1
• 229910000027 potassium carbonate Inorganic materials 0.000 description 1
• 239000000843 powder Substances 0.000 description 1
• 239000002244 precipitate Substances 0.000 description 1
• 230000009257 reactivity Effects 0.000 description 1
• 238000007127 saponification reaction Methods 0.000 description 1
• 229910052709 silver Inorganic materials 0.000 description 1
• 239000004332 silver Substances 0.000 description 1
• 239000004289 sodium hydrogen sulphite Substances 0.000 description 1
• 239000007858 starting material Substances 0.000 description 1
• 238000000859 sublimation Methods 0.000 description 1
• 230000008022 sublimation Effects 0.000 description 1
• LBLYYCQCTBFVLH-UHFFFAOYSA-M toluenesulfonate group Chemical group C=1(C(=CC=CC1)S(=O)(=O)[O-])C LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
• 238000000844 transformation Methods 0.000 description 1
• 230000007704 transition Effects 0.000 description 1
• 238000010626 work up procedure Methods 0.000 description 1