RU2060257C1 - Способ получения гидрокортизона, соединения в качестве промежуточных продуктов в синтезе гидрокортизона - Google Patents
Способ получения гидрокортизона, соединения в качестве промежуточных продуктов в синтезе гидрокортизона Download PDFInfo
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- RU2060257C1 RU2060257C1 SU925052452A SU5052452A RU2060257C1 RU 2060257 C1 RU2060257 C1 RU 2060257C1 SU 925052452 A SU925052452 A SU 925052452A SU 5052452 A SU5052452 A SU 5052452A RU 2060257 C1 RU2060257 C1 RU 2060257C1
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 47
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 title claims abstract description 22
- 229960000890 hydrocortisone Drugs 0.000 title claims abstract description 11
- 230000015572 biosynthetic process Effects 0.000 title claims description 9
- 238000003786 synthesis reaction Methods 0.000 title claims description 9
- 239000013067 intermediate product Substances 0.000 title claims description 4
- 238000004519 manufacturing process Methods 0.000 title description 5
- 238000000034 method Methods 0.000 claims abstract description 19
- 150000003944 halohydrins Chemical class 0.000 claims abstract description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical group CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 34
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical group O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 22
- 239000000047 product Substances 0.000 claims description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 18
- 239000002253 acid Substances 0.000 claims description 15
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 12
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 10
- 239000000460 chlorine Substances 0.000 claims description 10
- 229910052801 chlorine Inorganic materials 0.000 claims description 10
- 238000006462 rearrangement reaction Methods 0.000 claims description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 8
- 229910052794 bromium Inorganic materials 0.000 claims description 7
- 150000005846 sugar alcohols Polymers 0.000 claims description 7
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 6
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 6
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 claims description 6
- 229910052740 iodine Inorganic materials 0.000 claims description 6
- 239000002841 Lewis acid Substances 0.000 claims description 5
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
- 150000004662 dithiols Chemical class 0.000 claims description 5
- 239000000543 intermediate Substances 0.000 claims description 5
- 239000011630 iodine Substances 0.000 claims description 5
- 150000007517 lewis acids Chemical class 0.000 claims description 5
- 230000008707 rearrangement Effects 0.000 claims description 5
- 238000010992 reflux Methods 0.000 claims description 5
- DHBXNPKRAUYBTH-UHFFFAOYSA-N 1,1-ethanedithiol Chemical compound CC(S)S DHBXNPKRAUYBTH-UHFFFAOYSA-N 0.000 claims description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 4
- 230000000903 blocking effect Effects 0.000 claims description 4
- 230000003197 catalytic effect Effects 0.000 claims description 4
- 239000003153 chemical reaction reagent Substances 0.000 claims description 4
- 239000003638 chemical reducing agent Substances 0.000 claims description 4
- 238000006735 epoxidation reaction Methods 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 150000003573 thiols Chemical class 0.000 claims description 4
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 claims description 4
- 229910015900 BF3 Inorganic materials 0.000 claims description 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 3
- 230000002378 acidificating effect Effects 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 239000006184 cosolvent Substances 0.000 claims description 3
- 239000012259 ether extract Substances 0.000 claims description 3
- 229910000042 hydrogen bromide Inorganic materials 0.000 claims description 3
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical group II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 3
- 239000004593 Epoxy Substances 0.000 claims description 2
- 238000009835 boiling Methods 0.000 claims description 2
- 238000010511 deprotection reaction Methods 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 2
- 239000011707 mineral Substances 0.000 claims description 2
- 239000007800 oxidant agent Substances 0.000 claims description 2
- 150000004965 peroxy acids Chemical class 0.000 claims description 2
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 claims description 2
- 239000011701 zinc Substances 0.000 claims description 2
- 229910052725 zinc Inorganic materials 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 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 claims 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 2
- 239000001301 oxygen Substances 0.000 claims 2
- 229910052760 oxygen Inorganic materials 0.000 claims 2
- 239000003223 protective agent Substances 0.000 claims 2
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical group [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 claims 1
- 125000003710 aryl alkyl group Chemical group 0.000 claims 1
- 125000001246 bromo group Chemical group Br* 0.000 claims 1
- 125000004494 ethyl ester group Chemical group 0.000 claims 1
- 150000004820 halides Chemical class 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 230000007062 hydrolysis Effects 0.000 claims 1
- 238000006460 hydrolysis reaction Methods 0.000 claims 1
- 125000006239 protecting group Chemical group 0.000 claims 1
- 229910052736 halogen Inorganic materials 0.000 abstract description 2
- 125000005843 halogen group Chemical class 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 48
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- 239000000203 mixture Substances 0.000 description 16
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 14
- 235000019439 ethyl acetate Nutrition 0.000 description 11
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
- 238000010521 absorption reaction Methods 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 239000013078 crystal Substances 0.000 description 7
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 7
- 239000000377 silicon dioxide Substances 0.000 description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000011261 inert gas Substances 0.000 description 6
- 239000012044 organic layer Substances 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- RZRPTBIGEANTGU-UHFFFAOYSA-N -Androst-4-ene-3,11,17-trione Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)=O)C4C3CCC2=C1 RZRPTBIGEANTGU-UHFFFAOYSA-N 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- RZRPTBIGEANTGU-IRIMSJTPSA-N adrenosterone Chemical compound O=C1CC[C@]2(C)[C@H]3C(=O)C[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 RZRPTBIGEANTGU-IRIMSJTPSA-N 0.000 description 4
- 125000004122 cyclic group Chemical group 0.000 description 4
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 4
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 3
- 238000002329 infrared spectrum Methods 0.000 description 3
- -1 lithium aluminum hydride Chemical compound 0.000 description 3
- 150000004702 methyl esters Chemical class 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- HRRDCWDFRIJIQZ-UHFFFAOYSA-N naphthalene-1,8-dicarboxylic acid Chemical compound C1=CC(C(O)=O)=C2C(C(=O)O)=CC=CC2=C1 HRRDCWDFRIJIQZ-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 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 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 239000011260 aqueous acid Substances 0.000 description 2
- 150000001491 aromatic compounds Chemical class 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 150000004678 hydrides Chemical class 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 125000004430 oxygen atom Chemical group O* 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 2
- 235000019345 sodium thiosulphate Nutrition 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 239000011592 zinc chloride Substances 0.000 description 2
- 235000005074 zinc chloride Nutrition 0.000 description 2
- WLBJOUXPVHVXDG-CSMZCASVSA-N (8s,9s,10r,13s,14s)-11-hydroxy-17-(2-hydroxy-1-phenoxyethylidene)-10,13-dimethyl-2,6,7,8,9,11,12,14,15,16-decahydro-1h-cyclopenta[a]phenanthren-3-one Chemical compound C([C@H]1[C@H]2[C@@H]([C@]3(CCC(=O)C=C3CC2)C)C(O)C[C@@]11C)CC1=C(CO)OC1=CC=CC=C1 WLBJOUXPVHVXDG-CSMZCASVSA-N 0.000 description 1
- PQGPCHPAUPQLRJ-PJPBKAKHSA-N (8s,9s,10r,13s,14s,17r)-11-hydroxy-2'-(hydroxymethyl)-10,13-dimethyl-2'-phenoxyspiro[2,6,7,8,9,11,12,14,15,16-decahydro-1h-cyclopenta[a]phenanthrene-17,3'-oxirane]-3-one Chemical compound O([C@]12CC[C@H]3[C@H]4[C@@H]([C@]5(CCC(=O)C=C5CC4)C)C(O)C[C@@]31C)C2(CO)OC1=CC=CC=C1 PQGPCHPAUPQLRJ-PJPBKAKHSA-N 0.000 description 1
- PGGZAZHZNVKDLG-UHFFFAOYSA-N 1,4-dioxane;hexane Chemical compound CCCCCC.C1COCCO1 PGGZAZHZNVKDLG-UHFFFAOYSA-N 0.000 description 1
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 0 CC(CC1(C)C)(C(CC2)C(CC3)[C@@]1(C)[C@](*)(CCC1)C3=C1I)C2=O Chemical compound CC(CC1(C)C)(C(CC2)C(CC3)[C@@]1(C)[C@](*)(CCC1)C3=C1I)C2=O 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
- NOTFZGFABLVTIG-UHFFFAOYSA-N Cyclohexylethyl acetate Chemical compound CC(=O)OCCC1CCCCC1 NOTFZGFABLVTIG-UHFFFAOYSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- DOJXGHGHTWFZHK-UHFFFAOYSA-N Hexachloroacetone Chemical compound ClC(Cl)(Cl)C(=O)C(Cl)(Cl)Cl DOJXGHGHTWFZHK-UHFFFAOYSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 239000012448 Lithium borohydride Substances 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- HPXRVTGHNJAIIH-UHFFFAOYSA-N OC1CCCCC1 Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 238000010306 acid treatment Methods 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 125000000217 alkyl group Chemical group 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
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 229910052788 barium Inorganic materials 0.000 description 1
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
- 239000002585 base Substances 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
- 239000000872 buffer Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 150000004292 cyclic ethers Chemical class 0.000 description 1
- WBKFWQBXFREOFH-UHFFFAOYSA-N dichloromethane;ethyl acetate Chemical compound ClCCl.CCOC(C)=O WBKFWQBXFREOFH-UHFFFAOYSA-N 0.000 description 1
- BLEBFDYUDVZRFG-UHFFFAOYSA-N dichloromethane;propan-2-ol Chemical compound ClCCl.CC(C)O BLEBFDYUDVZRFG-UHFFFAOYSA-N 0.000 description 1
- YNLAOSYQHBDIKW-UHFFFAOYSA-M diethylaluminium chloride Chemical compound CC[Al](Cl)CC YNLAOSYQHBDIKW-UHFFFAOYSA-M 0.000 description 1
- 150000002009 diols Chemical class 0.000 description 1
- 150000002118 epoxides Chemical class 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- SJMLNDPIJZBEKY-UHFFFAOYSA-N ethyl 2,2,2-trichloroacetate Chemical compound CCOC(=O)C(Cl)(Cl)Cl SJMLNDPIJZBEKY-UHFFFAOYSA-N 0.000 description 1
- OAMZXMDZZWGPMH-UHFFFAOYSA-N ethyl acetate;toluene Chemical compound CCOC(C)=O.CC1=CC=CC=C1 OAMZXMDZZWGPMH-UHFFFAOYSA-N 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- OSVMTWJCGUFAOD-KZQROQTASA-N formestane Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1O OSVMTWJCGUFAOD-KZQROQTASA-N 0.000 description 1
- VBZWSGALLODQNC-UHFFFAOYSA-N hexafluoroacetone Chemical compound FC(F)(F)C(=O)C(F)(F)F VBZWSGALLODQNC-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 229910003002 lithium salt Inorganic materials 0.000 description 1
- 159000000002 lithium salts Chemical class 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-N phosphoric acid Substances OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000005185 salting out Methods 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
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 239000010937 tungsten Substances 0.000 description 1
- 229910052721 tungsten Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J5/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J21/00—Normal steroids containing carbon, hydrogen, halogen or oxygen having an oxygen-containing hetero ring spiro-condensed with the cyclopenta(a)hydrophenanthrene skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J13/00—Normal steroids containing carbon, hydrogen, halogen or oxygen having a carbon-to-carbon double bond from or to position 17
- C07J13/007—Normal steroids containing carbon, hydrogen, halogen or oxygen having a carbon-to-carbon double bond from or to position 17 with double bond in position 17 (20)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J33/00—Normal steroids having a sulfur-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton
- C07J33/005—Normal steroids having a sulfur-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton spiro-condensed
- C07J33/007—Cyclic thioketals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J5/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond
- C07J5/0046—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond substituted in position 17 alfa
- C07J5/0053—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond substituted in position 17 alfa not substituted in position 16
-
- 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)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Steroid Compounds (AREA)
- Enzymes And Modification Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR91-11052 | 1991-09-06 | ||
| FR9111052A FR2681069B1 (fr) | 1991-09-06 | 1991-09-06 | Nouveau procede de preparation de l'hydrocortisone et nouveaux intermediaires. |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| RU2060257C1 true RU2060257C1 (ru) | 1996-05-20 |
Family
ID=9416716
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SU925052452A RU2060257C1 (ru) | 1991-09-06 | 1992-08-21 | Способ получения гидрокортизона, соединения в качестве промежуточных продуктов в синтезе гидрокортизона |
Country Status (20)
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2683530B1 (fr) * | 1991-11-08 | 1994-01-21 | Roussel Uclaf | Nouveau procede de preparation de derives 20-oxo 17 alpha, 21-dihydroxyles du pregnane et nouveaux intermediaires. |
| FR2691968B1 (fr) * | 1992-06-04 | 1994-07-29 | Roussel Uclaf | Nouveau procede de preparation d'un derive sterouide 11-ceto. |
| FR2719588B1 (fr) * | 1994-05-03 | 1996-06-07 | Roussel Uclaf | Nouveau procédé de préparation de la substance "S" et nouveaux intermédiaires. |
| FR2721927B1 (fr) * | 1994-07-01 | 1996-08-09 | Roussel Uclaf | Nouveau procede de preparation de derives steroides 20-oxo 17 alpha, 21-dihydroxyles et nouveaux intermediaires |
| US5929262A (en) * | 1995-03-30 | 1999-07-27 | The United States Of America As Represented By The Department Of Health And Human Services | Method for preparing 17α-acetoxy-11β-(4-N, N-dimethylaminophyl)-19-Norpregna-4,9-diene-3, 20-dione, intermediates useful in the method, and methods for the preparation of such intermediates |
| US6528652B1 (en) | 1999-01-21 | 2003-03-04 | Chronimed | Composition and device for detecting leukocytes in urine |
| US6348324B1 (en) | 1999-01-21 | 2002-02-19 | Hypoguard America Limited | Composition and device for detecting leukocytes in urine |
| US8990064B2 (en) * | 2009-07-28 | 2015-03-24 | Language Weaver, Inc. | Translating documents based on content |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2744110A (en) * | 1954-04-22 | 1956-05-01 | Searle & Co | 3-ethylene mercaptole derivatives of progesterone |
| GB1089788A (en) * | 1965-07-07 | 1967-11-08 | Parke Davis & Co | Process for the production of steroidal lactone compounds and intermediates thereof |
| NL7607283A (nl) * | 1975-07-23 | 1977-01-25 | Merck & Co Inc | Werkwijze voor het bereiden van nieuwe pregnaansteroiden. |
| FR2344286A1 (fr) * | 1976-03-16 | 1977-10-14 | Roussel Uclaf | Nouveaux derives 17-spirosultines, les g-hydroxy acides correspondants, leur procede de preparation et leur application comme medicament |
| US5182381A (en) * | 1982-03-01 | 1993-01-26 | Roussel Ulcaf | Intermediates for 3-keto-19-nor-Δ4,9 -steroids |
| EP0123734A1 (en) * | 1983-04-29 | 1984-11-07 | Gist-Brocades N.V. | 17-(Isocyano-sulfonylmethylene)-steroids, 17-(formamido-sulfonylmethylene)-steroids and their preparation |
| GB8721384D0 (en) * | 1987-09-11 | 1987-10-21 | Erba Farmitalia | 17-substituted andro-sta-1 4-dien-3-one derivatives |
| HU208437B (en) * | 1988-04-08 | 1993-10-28 | Roussel Uclaf | Process for producing 9-alpha-hydroxy- -17-methylene-steroides for synthetizing corticosteroides |
-
1991
- 1991-09-06 FR FR9111052A patent/FR2681069B1/fr not_active Expired - Fee Related
-
1992
- 1992-07-22 ZA ZA925516A patent/ZA925516B/xx unknown
- 1992-07-23 TW TW081105829A patent/TW269693B/zh not_active IP Right Cessation
- 1992-07-27 AU AU20570/92A patent/AU653841B2/en not_active Expired
- 1992-08-21 RU SU925052452A patent/RU2060257C1/ru active
- 1992-08-25 US US07/935,535 patent/US5260463A/en not_active Expired - Lifetime
- 1992-08-25 JP JP24713992A patent/JP3466645B2/ja not_active Expired - Lifetime
- 1992-09-03 DE DE69206721T patent/DE69206721T2/de not_active Expired - Lifetime
- 1992-09-03 EP EP92402406A patent/EP0531212B1/fr not_active Expired - Lifetime
- 1992-09-03 MX MX9205063A patent/MX9205063A/es unknown
- 1992-09-03 AT AT92402406T patent/ATE131488T1/de active
- 1992-09-03 DK DK92402406.0T patent/DK0531212T3/da active
- 1992-09-03 ES ES92402406T patent/ES2089449T3/es not_active Expired - Lifetime
- 1992-09-04 PL PL92319638A patent/PL173272B1/pl unknown
- 1992-09-04 PL PL92315569A patent/PL172822B1/pl unknown
- 1992-09-04 PL PL92295836A patent/PL172040B1/pl unknown
- 1992-09-04 CA CA002077625A patent/CA2077625C/fr not_active Expired - Lifetime
- 1992-09-04 HU HU9202851A patent/HU212666B/hu unknown
- 1992-09-04 PL PL92315567A patent/PL173589B1/pl unknown
- 1992-09-04 PL PL92315568A patent/PL172809B1/pl unknown
- 1992-09-05 KR KR1019920016242A patent/KR100220542B1/ko not_active Expired - Lifetime
- 1992-09-05 CN CN92110286A patent/CN1035947C/zh not_active Expired - Lifetime
-
1993
- 1993-06-18 UA UA93002997A patent/UA35556C2/uk unknown
- 1993-08-12 US US08/105,742 patent/US5401840A/en not_active Expired - Lifetime
-
1994
- 1994-12-22 US US08/362,120 patent/US5502182A/en not_active Expired - Lifetime
-
1995
- 1995-10-02 US US08/538,027 patent/US5556962A/en not_active Expired - Lifetime
- 1995-12-14 GR GR950401070T patent/GR3018402T3/el unknown
Non-Patent Citations (1)
| Title |
|---|
| Патент США N 3072684, кл. C 07 j 5/00, 1985. * |
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