BE414217A

BE414217A -

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Publication number: BE414217A
Authority: BE; Belgium
Prior art keywords: general formula; hydrogenation; unsaturated; diketone; saturated
Prior art date

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English (en)

French (fr)

Publication of BE414217A publication Critical patent/BE414217A/fr

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238000005984 hydrogenation reaction Methods 0.000 claims description 31
238000000034 method Methods 0.000 claims description 29
125000005594 diketone group Chemical group 0.000 claims description 24
229920006395 saturated elastomer Polymers 0.000 claims description 21
239000001257 hydrogen Substances 0.000 claims description 18
229910052739 hydrogen Inorganic materials 0.000 claims description 18
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
239000003795 chemical substances by application Substances 0.000 claims description 15
239000007858 starting material Substances 0.000 claims description 15
230000008569 process Effects 0.000 claims description 14
239000003054 catalyst Substances 0.000 claims description 9
230000009467 reduction Effects 0.000 claims description 9
RAJWOBJTTGJROA-RNQTWYFASA-N androstane-3,17-dione Chemical compound C1C(=O)CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC21 RAJWOBJTTGJROA-RNQTWYFASA-N 0.000 claims description 8
230000009471 action Effects 0.000 claims description 7
238000012986 modification Methods 0.000 claims description 7
230000000694 effects Effects 0.000 claims description 6
239000002253 acid Substances 0.000 claims description 4
230000015572 biosynthetic process Effects 0.000 claims description 4
QGXBDMJGAMFCBF-LUJOEAJASA-N epiandrosterone Chemical class C1[C@@H](O)CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC[C@H]21 QGXBDMJGAMFCBF-LUJOEAJASA-N 0.000 claims description 4
230000003647 oxidation Effects 0.000 claims description 4
238000007254 oxidation reaction Methods 0.000 claims description 4
230000002378 acidificating effect Effects 0.000 claims description 3
FMGSKLZLMKYGDP-USOAJAOKSA-N dehydroepiandrosterone Chemical compound C1[C@@H](O)CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC=C21 FMGSKLZLMKYGDP-USOAJAOKSA-N 0.000 claims description 3
229910052736 halogen Inorganic materials 0.000 claims description 3
GPRLSGONYQIRFK-UHFFFAOYSA-N hydron Chemical compound [H+] GPRLSGONYQIRFK-UHFFFAOYSA-N 0.000 claims description 3
229960002847 prasterone Drugs 0.000 claims description 3
229910052782 aluminium Inorganic materials 0.000 claims description 2
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 2
150000002367 halogens Chemical class 0.000 claims description 2
229910052751 metal Inorganic materials 0.000 claims description 2
239000002184 metal Substances 0.000 claims description 2
230000001590 oxidative effect Effects 0.000 claims description 2
238000012937 correction Methods 0.000 claims 1
XOVJAYNMQDTIJD-UHFFFAOYSA-N cyclopentobarbital Chemical compound C1CC=CC1C1(CC=C)C(=O)NC(=O)NC1=O XOVJAYNMQDTIJD-UHFFFAOYSA-N 0.000 claims 1
150000004820 halides Chemical class 0.000 claims 1
150000002987 phenanthrenes Chemical class 0.000 claims 1
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 22
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 16
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
235000019441 ethanol Nutrition 0.000 description 10
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
229960000583 acetic acid Drugs 0.000 description 8
239000012362 glacial acetic acid Substances 0.000 description 8
AEMFNILZOJDQLW-QAGGRKNESA-N androst-4-ene-3,17-dione Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 AEMFNILZOJDQLW-QAGGRKNESA-N 0.000 description 7
239000000203 mixture Substances 0.000 description 7
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
229910052799 carbon Inorganic materials 0.000 description 6
238000006243 chemical reaction Methods 0.000 description 6
150000002431 hydrogen Chemical class 0.000 description 6
230000009466 transformation Effects 0.000 description 6
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
UURSGYCYDHBXDS-CIMZGTONSA-N (8R,9S,10R,13R,14S)-10,13-dimethyl-2,3,6,7,8,9,11,12,14,17-decahydro-1H-cyclopenta[a]phenanthrene-15,16-dione Chemical compound [C@@H]12C(C(C[C@@]1(C)CC[C@H]1[C@H]2CCC2=CCCC[C@]12C)=O)=O UURSGYCYDHBXDS-CIMZGTONSA-N 0.000 description 5
229940061641 androsterone Drugs 0.000 description 5
238000001704 evaporation Methods 0.000 description 5
239000003163 gonadal steroid hormone Substances 0.000 description 5
BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 4
230000008020 evaporation Effects 0.000 description 4
238000002844 melting Methods 0.000 description 4
230000008018 melting Effects 0.000 description 4
230000001766 physiological effect Effects 0.000 description 4
239000000047 product Substances 0.000 description 4
239000000126 substance Substances 0.000 description 4
QGXBDMJGAMFCBF-HLUDHZFRSA-N 5α-Androsterone Chemical compound C1[C@H](O)CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC[C@H]21 QGXBDMJGAMFCBF-HLUDHZFRSA-N 0.000 description 3
QGXBDMJGAMFCBF-UHFFFAOYSA-N Etiocholanolone Natural products C1C(O)CCC2(C)C3CCC(C)(C(CC4)=O)C4C3CCC21 QGXBDMJGAMFCBF-UHFFFAOYSA-N 0.000 description 3
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
150000001875 compounds Chemical class 0.000 description 3
238000002425 crystallisation Methods 0.000 description 3
230000008025 crystallization Effects 0.000 description 3
238000004821 distillation Methods 0.000 description 3
230000004048 modification Effects 0.000 description 3
239000002904 solvent Substances 0.000 description 3
QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
QRLVDLBMBULFAL-UHFFFAOYSA-N Digitonin Natural products CC1CCC2(OC1)OC3C(O)C4C5CCC6CC(OC7OC(CO)C(OC8OC(CO)C(O)C(OC9OCC(O)C(O)C9OC%10OC(CO)C(O)C(OC%11OC(CO)C(O)C(O)C%11O)C%10O)C8O)C(O)C7O)C(O)CC6(C)C5CCC4(C)C3C2C QRLVDLBMBULFAL-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
230000001476 alcoholic effect Effects 0.000 description 2
KRVSOGSZCMJSLX-UHFFFAOYSA-L chromic acid Substances O[Cr](O)(=O)=O KRVSOGSZCMJSLX-UHFFFAOYSA-L 0.000 description 2
238000001816 cooling Methods 0.000 description 2
UVYVLBIGDKGWPX-KUAJCENISA-N digitonin Chemical compound O([C@@H]1[C@@H]([C@]2(CC[C@@H]3[C@@]4(C)C[C@@H](O)[C@H](O[C@H]5[C@@H]([C@@H](O)[C@@H](O[C@H]6[C@@H]([C@@H](O[C@H]7[C@@H]([C@@H](O)[C@H](O)CO7)O)[C@H](O)[C@@H](CO)O6)O[C@H]6[C@@H]([C@@H](O[C@H]7[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O7)O)[C@@H](O)[C@@H](CO)O6)O)[C@@H](CO)O5)O)C[C@@H]4CC[C@H]3[C@@H]2[C@@H]1O)C)[C@@H]1C)[C@]11CC[C@@H](C)CO1 UVYVLBIGDKGWPX-KUAJCENISA-N 0.000 description 2
UVYVLBIGDKGWPX-UHFFFAOYSA-N digitonine Natural products CC1C(C2(CCC3C4(C)CC(O)C(OC5C(C(O)C(OC6C(C(OC7C(C(O)C(O)CO7)O)C(O)C(CO)O6)OC6C(C(OC7C(C(O)C(O)C(CO)O7)O)C(O)C(CO)O6)O)C(CO)O5)O)CC4CCC3C2C2O)C)C2OC11CCC(C)CO1 UVYVLBIGDKGWPX-UHFFFAOYSA-N 0.000 description 2
238000001035 drying Methods 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
239000012467 final product Substances 0.000 description 2
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 2
125000000468 ketone group Chemical group 0.000 description 2
238000004519 manufacturing process Methods 0.000 description 2
230000007935 neutral effect Effects 0.000 description 2
MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 2
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
229910003446 platinum oxide Inorganic materials 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
238000002360 preparation method Methods 0.000 description 2
238000000746 purification Methods 0.000 description 2
239000011541 reaction mixture Substances 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
239000011734 sodium Substances 0.000 description 2
235000011121 sodium hydroxide Nutrition 0.000 description 2
CBMYJHIOYJEBSB-DYSINSMMSA-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-3,17-diol Chemical class C1C(O)CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CC[C@H]21 CBMYJHIOYJEBSB-DYSINSMMSA-N 0.000 description 1
QZLYKIGBANMMBK-UGCZWRCOSA-N 5α-Androstane Chemical compound C([C@@H]1CC2)CCC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CCC[C@@]2(C)CC1 QZLYKIGBANMMBK-UGCZWRCOSA-N 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
QPLDLSVMHZLSFG-UHFFFAOYSA-N Copper oxide Chemical compound [Cu]=O QPLDLSVMHZLSFG-UHFFFAOYSA-N 0.000 description 1
239000005751 Copper oxide Substances 0.000 description 1
YZCKVEUIGOORGS-UHFFFAOYSA-N Hydrogen atom Chemical compound [H] YZCKVEUIGOORGS-UHFFFAOYSA-N 0.000 description 1
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 1
GCKMFJBGXUYNAG-HLXURNFRSA-N Methyltestosterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@](C)(O)[C@@]1(C)CC2 GCKMFJBGXUYNAG-HLXURNFRSA-N 0.000 description 1
PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 1
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
239000003513 alkali Substances 0.000 description 1
SMZOGRDCAXLAAR-UHFFFAOYSA-N aluminium isopropoxide Chemical compound [Al+3].CC(C)[O-].CC(C)[O-].CC(C)[O-] SMZOGRDCAXLAAR-UHFFFAOYSA-N 0.000 description 1
150000008064 anhydrides Chemical class 0.000 description 1
238000009835 boiling Methods 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
229910000431 copper oxide Inorganic materials 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
229940079593 drug Drugs 0.000 description 1
239000003814 drug Substances 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
150000002440 hydroxy compounds Chemical class 0.000 description 1
239000013067 intermediate product Substances 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
239000000155 melt Substances 0.000 description 1
229960001566 methyltestosterone Drugs 0.000 description 1
239000007800 oxidant agent Substances 0.000 description 1
125000004430 oxygen atom Chemical group O* 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
239000001397 quillaja saponaria molina bark Substances 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
238000005057 refrigeration Methods 0.000 description 1
229930182490 saponin Natural products 0.000 description 1
150000007949 saponins Chemical class 0.000 description 1
125000003198 secondary alcohol group Chemical group 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
238000003756 stirring Methods 0.000 description 1
238000004448 titration Methods 0.000 description 1
210000002700 urine Anatomy 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
239000011701 zinc Substances 0.000 description 1