BE537740A - - Google Patents

Info

Publication number

BE537740A

BE537740A BE537740DA BE537740A BE 537740 A BE537740 A BE 537740A BE 537740D A BE537740D A BE 537740DA BE 537740 A BE537740 A BE 537740A

Authority

BE

Belgium

Prior art keywords

oxo

spirostan

process according

alkali

hecogenin

Prior art date

Links

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• QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 37
• WFDIJRYMOXRFFG-UHFFFAOYSA-N acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 20
• HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 18
• JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 14
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 13
• 238000000034 method Methods 0.000 claims description 13
• 239000003513 alkali Substances 0.000 claims description 12
• QTBSBXVTEAMEQO-UHFFFAOYSA-M acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 10
• KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 10
• HCHKCACWOHOZIP-UHFFFAOYSA-N zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 10
• 239000002904 solvent Substances 0.000 claims description 9
• 238000010438 heat treatment Methods 0.000 claims description 8
• 238000002360 preparation method Methods 0.000 claims description 8
• QOLRLLFJMZLYQJ-GSSCIUJHSA-N Hecogenin Natural products O=C1[C@]2(C)[C@H]3[C@H](C)[C@@]4(O[C@H]3C[C@H]2[C@@H]2[C@@H]([C@]3(C)[C@H](C[C@@H](O)CC3)CC2)C1)OC[C@H](C)CC4 QOLRLLFJMZLYQJ-GSSCIUJHSA-N 0.000 claims description 6
• 239000003518 caustics Substances 0.000 claims description 6
• 239000011701 zinc Substances 0.000 claims description 6
• 229910052725 zinc Inorganic materials 0.000 claims description 6
• QOLRLLFJMZLYQJ-LOBDNJQFSA-N Hecogenin Chemical compound O([C@@H]1[C@@H]([C@]2(C(=O)C[C@@H]3[C@@]4(C)CC[C@H](O)C[C@@H]4CC[C@H]3[C@@H]2C1)C)[C@@H]1C)[C@]11CC[C@@H](C)CO1 QOLRLLFJMZLYQJ-LOBDNJQFSA-N 0.000 claims description 5
• 238000009835 boiling Methods 0.000 claims description 4
• 150000002148 esters Chemical class 0.000 claims description 4
• 239000007858 starting material Substances 0.000 claims description 4
• 238000005886 esterification reaction Methods 0.000 claims description 3
• -1 hecogenin ester Chemical class 0.000 claims description 3
• 238000006460 hydrolysis reaction Methods 0.000 claims description 3
• 239000000126 substance Substances 0.000 claims 2
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 25
• 238000010992 reflux Methods 0.000 description 20
• 239000000047 product Substances 0.000 description 17
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
• 229960000583 Acetic Acid Drugs 0.000 description 14
• OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 14
• 238000006243 chemical reaction Methods 0.000 description 10
• 150000001875 compounds Chemical class 0.000 description 10
• 235000019441 ethanol Nutrition 0.000 description 9
• 238000001914 filtration Methods 0.000 description 8
• DKGAVHZHDRPRBM-UHFFFAOYSA-N t-BuOH Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 8
• 238000002844 melting Methods 0.000 description 7
• 239000000203 mixture Substances 0.000 description 7
• 238000003756 stirring Methods 0.000 description 7
• 239000012043 crude product Substances 0.000 description 6
• NDXLVXDHVHWYFR-UHFFFAOYSA-N 2-pyridin-1-ium-1-ylacetohydrazide;chloride Chemical compound [Cl-].NNC(=O)C[N+]1=CC=CC=C1 NDXLVXDHVHWYFR-UHFFFAOYSA-N 0.000 description 5
• CVKZWRTYHCDWTE-RSEFXUKDSA-N Hecogenin acetate Chemical compound O([C@@H]1[C@@H]([C@]2(C(=O)C[C@@H]3[C@@]4(C)CC[C@@H](C[C@@H]4CC[C@H]3[C@@H]2C1)OC(C)=O)C)[C@@H]1C)[C@]11CC[C@@H](C)CO1 CVKZWRTYHCDWTE-RSEFXUKDSA-N 0.000 description 5
• 230000005712 crystallization Effects 0.000 description 5
• 238000006640 acetylation reaction Methods 0.000 description 4
• 238000005893 bromination reaction Methods 0.000 description 4
• HEDRZPFGACZZDS-UHFFFAOYSA-N chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
• 238000002425 crystallisation Methods 0.000 description 4
• RTZKZFJDLAIYFH-UHFFFAOYSA-N diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
• 238000004821 distillation Methods 0.000 description 4
• 239000012362 glacial acetic acid Substances 0.000 description 4
• 239000000463 material Substances 0.000 description 4
• LRHPLDYGYMQRHN-UHFFFAOYSA-N n-butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
• 239000002244 precipitate Substances 0.000 description 4
• 239000002253 acid Substances 0.000 description 3
• WKBOTKDWSSQWDR-UHFFFAOYSA-N bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
• 239000000706 filtrate Substances 0.000 description 3
• 239000007787 solid Substances 0.000 description 3
• MFYSYFVPBJMHGN-ZPOLXVRWSA-N Cortisone Chemical compound O=C1CC[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 MFYSYFVPBJMHGN-ZPOLXVRWSA-N 0.000 description 2
• UIIMBOGNXHQVGW-UHFFFAOYSA-M NaHCO3 Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
• 241001272996 Polyphylla fullo Species 0.000 description 2
• 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 2
• 238000007792 addition Methods 0.000 description 2
• 230000015572 biosynthetic process Effects 0.000 description 2
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
• 238000001816 cooling Methods 0.000 description 2
• 229960004544 cortisone Drugs 0.000 description 2
• 238000003306 harvesting Methods 0.000 description 2
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
• 238000004519 manufacturing process Methods 0.000 description 2
• KEAYESYHFKHZAL-UHFFFAOYSA-N sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
• 229910052708 sodium Inorganic materials 0.000 description 2
• 239000011734 sodium Substances 0.000 description 2
• 239000011343 solid material Substances 0.000 description 2
• 239000000725 suspension Substances 0.000 description 2
• 238000003786 synthesis reaction Methods 0.000 description 2
• 230000002194 synthesizing Effects 0.000 description 2
• BTANRVKWQNVYAZ-UHFFFAOYSA-N 2-Butanol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 1
• SXPWTBGAZSPLHA-UHFFFAOYSA-M Cetalkonium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 SXPWTBGAZSPLHA-UHFFFAOYSA-M 0.000 description 1
• WHXGJDDMDMRMBZ-UHFFFAOYSA-M [Br+].C(C)(=O)[O-] Chemical compound [Br+].C(C)(=O)[O-] WHXGJDDMDMRMBZ-UHFFFAOYSA-M 0.000 description 1
• 239000008346 aqueous phase Substances 0.000 description 1
• 239000007900 aqueous suspension Substances 0.000 description 1
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
• 239000007795 chemical reaction product Substances 0.000 description 1
• 230000000875 corresponding Effects 0.000 description 1
• 238000007865 diluting Methods 0.000 description 1
• 238000010790 dilution Methods 0.000 description 1
• 230000000694 effects Effects 0.000 description 1
• 238000003379 elimination reaction Methods 0.000 description 1
• 239000012259 ether extract Substances 0.000 description 1
• 239000000284 extract Substances 0.000 description 1
• 230000002349 favourable Effects 0.000 description 1
• PEDCQBHIVMGVHV-UHFFFAOYSA-N glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 1
• 229910052736 halogen Inorganic materials 0.000 description 1
• 150000002367 halogens Chemical class 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-N hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
• 230000003301 hydrolyzing Effects 0.000 description 1
• XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxyl anion Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
• 229940072033 potash Drugs 0.000 description 1
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 1
• 235000015320 potassium carbonate Nutrition 0.000 description 1
• 238000000746 purification Methods 0.000 description 1
• 235000017557 sodium bicarbonate Nutrition 0.000 description 1
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
• INLFWQCRAJUDCR-LYLBMTSKSA-N spirostane Chemical compound O([C@@H]1[C@@H]([C@]2(CC[C@@H]3[C@@]4(C)CCCCC4CC[C@H]3[C@@H]2C1)C)[C@@H]1C)[C@]11CC[C@@H](C)CO1 INLFWQCRAJUDCR-LYLBMTSKSA-N 0.000 description 1