BE563650A

BE563650A -

Info

Publication number: BE563650A
Authority: BE; Belgium
Prior art keywords: bismethylenedioxy; dione; acid; steroid; pregnene
Prior art date

Application number

Other languages

English (en)

French (fr)

Publication of BE563650A publication Critical patent/BE563650A/fr

Links

238000000034 method Methods 0.000 claims description 27
QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 25
150000003431 steroids Chemical class 0.000 claims description 25
VEXZGXHMUGYJMC-UHFFFAOYSA-N HCl Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 14
239000002253 acid Substances 0.000 claims description 13
BDAGIHXWWSANSR-UHFFFAOYSA-N formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 12
150000003128 pregnanes Chemical class 0.000 claims description 9
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 7
VLTRZXGMWDSKGL-UHFFFAOYSA-N Perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 claims description 6
235000019253 formic acid Nutrition 0.000 claims description 4
XOFYZVNMUHMLCC-ZPOLXVRWSA-N Prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 claims description 2
229960004618 prednisone Drugs 0.000 claims 1
UIIMBOGNXHQVGW-UHFFFAOYSA-M NaHCO3 Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 17
HEDRZPFGACZZDS-UHFFFAOYSA-N chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
239000000203 mixture Substances 0.000 description 16
YMWUJEATGCHHMB-UHFFFAOYSA-N methylene dichloride Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 14
238000006243 chemical reaction Methods 0.000 description 11
239000000243 solution Substances 0.000 description 11
WFDIJRYMOXRFFG-UHFFFAOYSA-N acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 10
JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
-1 steroid compounds Chemical class 0.000 description 10
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
229960000583 Acetic Acid Drugs 0.000 description 9
XEKOWRVHYACXOJ-UHFFFAOYSA-N acetic acid ethyl ester Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
150000001875 compounds Chemical class 0.000 description 9
239000002904 solvent Substances 0.000 description 9
OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 8
235000017557 sodium bicarbonate Nutrition 0.000 description 8
229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
CSCPPACGZOOCGX-UHFFFAOYSA-N acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
239000000284 extract Substances 0.000 description 6
CSNNHWWHGAXBCP-UHFFFAOYSA-L mgso4 Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
UOQFZGVGGMHGEE-UHFFFAOYSA-N 1,1-dihydroxypropan-2-one Chemical group CC(=O)C(O)O UOQFZGVGGMHGEE-UHFFFAOYSA-N 0.000 description 5
125000004432 carbon atoms Chemical group C* 0.000 description 5
229960003290 cortisone acetate Drugs 0.000 description 5
ITRJWOMZKQRYTA-RFZYENFJSA-N Cortisone acetate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)COC(=O)C)(O)[C@@]1(C)CC2=O ITRJWOMZKQRYTA-RFZYENFJSA-N 0.000 description 4
210000004940 Nucleus Anatomy 0.000 description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-M acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
WSFSSNUMVMOOMR-UHFFFAOYSA-N formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
239000012362 glacial acetic acid Substances 0.000 description 4
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
239000007858 starting material Substances 0.000 description 4
PNEYBMLMFCGWSK-UHFFFAOYSA-N AI2O3 Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 3
150000001299 aldehydes Chemical class 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
239000003153 chemical reaction reagent Substances 0.000 description 3
238000005755 formation reaction Methods 0.000 description 3
238000006460 hydrolysis reaction Methods 0.000 description 3
229910052943 magnesium sulfate Inorganic materials 0.000 description 3
235000019341 magnesium sulphate Nutrition 0.000 description 3
239000012071 phase Substances 0.000 description 3
239000000047 product Substances 0.000 description 3
239000011541 reaction mixture Substances 0.000 description 3
238000002407 reforming Methods 0.000 description 3
125000001424 substituent group Chemical group 0.000 description 3
SVYCRJXQZUCUND-PQXSVQADSA-N (6S,8S,9S,10R,13S,14S,17R)-17-hydroxy-17-(2-hydroxyacetyl)-6,10,13-trimethyl-6,7,8,9,12,14,15,16-octahydrocyclopenta[a]phenanthrene-3,11-dione Chemical compound C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2C(=O)C[C@]2(C)[C@@](O)(C(=O)CO)CC[C@H]21 SVYCRJXQZUCUND-PQXSVQADSA-N 0.000 description 2
JYGXADMDTFJGBT-VWUMJDOOSA-N Cortisol 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 description 2
RXKJFZQQPQGTFL-UHFFFAOYSA-N Dihydroxyacetone Chemical compound OCC(=O)CO RXKJFZQQPQGTFL-UHFFFAOYSA-N 0.000 description 2
229940120503 Dihydroxyacetone Drugs 0.000 description 2
IKHGUXGNUITLKF-UHFFFAOYSA-N acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
239000012445 acidic reagent Substances 0.000 description 2
150000007933 aliphatic carboxylic acids Chemical class 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
229910052799 carbon Inorganic materials 0.000 description 2
239000007810 chemical reaction solvent Substances 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
ALEXXDVDDISNDU-JZYPGELDSA-N cortisol 21-acetate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)COC(=O)C)(O)[C@@]1(C)C[C@@H]2O ALEXXDVDDISNDU-JZYPGELDSA-N 0.000 description 2
230000000694 effects Effects 0.000 description 2
238000001704 evaporation Methods 0.000 description 2
239000000727 fraction Substances 0.000 description 2
229960000890 hydrocortisone Drugs 0.000 description 2
229960001067 hydrocortisone acetate Drugs 0.000 description 2
125000004435 hydrogen atoms Chemical group [H]* 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
239000003960 organic solvent Substances 0.000 description 2
238000000746 purification Methods 0.000 description 2
239000000725 suspension Substances 0.000 description 2
SFUVLEGIZGPPNN-UHFFFAOYSA-N (2-pyridin-2-ylacetyl) 2-pyridin-2-ylacetate Chemical compound C=1C=CC=NC=1CC(=O)OC(=O)CC1=CC=CC=N1 SFUVLEGIZGPPNN-UHFFFAOYSA-N 0.000 description 1
ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 1-butanal Chemical compound CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 1
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 1
150000000795 D-homosteroids Chemical class 0.000 description 1
238000003747 Grignard reaction Methods 0.000 description 1
JARKCYVAAOWBJS-UHFFFAOYSA-N Hexanal Chemical compound CCCCCC=O JARKCYVAAOWBJS-UHFFFAOYSA-N 0.000 description 1
HGBOYTHUEUWSSQ-UHFFFAOYSA-N Pentanal Chemical compound CCCCC=O HGBOYTHUEUWSSQ-UHFFFAOYSA-N 0.000 description 1
LRJOMUJRLNCICJ-JZYPGELDSA-N Prednisolone acetate Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)COC(=O)C)(O)[C@@]1(C)C[C@@H]2O LRJOMUJRLNCICJ-JZYPGELDSA-N 0.000 description 1
235000011054 acetic acid Nutrition 0.000 description 1
150000001242 acetic acid derivatives Chemical class 0.000 description 1
238000006640 acetylation reaction Methods 0.000 description 1
238000005903 acid hydrolysis reaction Methods 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
230000004075 alteration Effects 0.000 description 1
239000011260 aqueous acid Substances 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
239000002026 chloroform extract Substances 0.000 description 1
239000002036 chloroform fraction Substances 0.000 description 1
QSKWJTXWJJOJFP-UHFFFAOYSA-N chloroform;ethoxyethane Chemical compound ClC(Cl)Cl.CCOCC QSKWJTXWJJOJFP-UHFFFAOYSA-N 0.000 description 1
239000012141 concentrate Substances 0.000 description 1
238000009833 condensation Methods 0.000 description 1
230000005494 condensation Effects 0.000 description 1
238000001816 cooling Methods 0.000 description 1
230000000875 corresponding Effects 0.000 description 1
MOVRKLZUVNCBIP-RFZYENFJSA-N cortancyl Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)COC(=O)C)(O)[C@@]1(C)CC2=O MOVRKLZUVNCBIP-RFZYENFJSA-N 0.000 description 1
229960004544 cortisone Drugs 0.000 description 1
150000001887 cortisones Chemical class 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000005712 crystallization Effects 0.000 description 1
238000001035 drying Methods 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
239000002024 ethyl acetate extract Substances 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
239000008241 heterogeneous mixture Substances 0.000 description 1
KJUGUADJHNHALS-UHFFFAOYSA-O hydron;2H-tetrazole Chemical compound C1=NN=[NH+]N1 KJUGUADJHNHALS-UHFFFAOYSA-O 0.000 description 1
229910052500 inorganic mineral Chemical class 0.000 description 1
239000000463 material Substances 0.000 description 1
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
239000011707 mineral Chemical class 0.000 description 1
235000010755 mineral Nutrition 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
235000011007 phosphoric acid Nutrition 0.000 description 1
150000003016 phosphoric acids Chemical class 0.000 description 1
229960002800 prednisolone acetate Drugs 0.000 description 1
238000002360 preparation method Methods 0.000 description 1
NBBJYMSMWIIQGU-UHFFFAOYSA-N propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
238000010992 reflux Methods 0.000 description 1
230000008929 regeneration Effects 0.000 description 1
238000011069 regeneration method Methods 0.000 description 1
239000012047 saturated solution Substances 0.000 description 1
239000011265 semifinished product Substances 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000012086 standard solution Substances 0.000 description 1
238000003756 stirring Methods 0.000 description 1
238000000844 transformation Methods 0.000 description 1
230000001131 transforming Effects 0.000 description 1