BE430451A - - Google Patents

Info

Publication number

BE430451A

BE430451A BE430451DA BE430451A BE 430451 A BE430451 A BE 430451A BE 430451D A BE430451D A BE 430451DA BE 430451 A BE430451 A BE 430451A

Authority

BE

Belgium

Prior art keywords

ether

alcohol

solution

water

reaction

Prior art date

Links

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• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 48
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 42
• 235000019441 ethanol Nutrition 0.000 description 31
• 239000000243 solution Substances 0.000 description 29
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 25
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 22
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
• 238000000034 method Methods 0.000 description 19
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 18
• MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 18
• 238000006243 chemical reaction Methods 0.000 description 18
• 238000002844 melting Methods 0.000 description 18
• 230000008018 melting Effects 0.000 description 18
• 239000000047 product Substances 0.000 description 17
• 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 11
• 230000001476 alcoholic effect Effects 0.000 description 11
• 239000003795 chemical substances by application Substances 0.000 description 11
• 229910052708 sodium Inorganic materials 0.000 description 11
• 239000011734 sodium Substances 0.000 description 11
• 229960003604 testosterone Drugs 0.000 description 11
• 239000013078 crystal Substances 0.000 description 9
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 9
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
• 238000002425 crystallisation Methods 0.000 description 8
• 230000008025 crystallization Effects 0.000 description 8
• -1 for example Chemical class 0.000 description 7
• 238000010438 heat treatment Methods 0.000 description 7
• 150000002576 ketones Chemical class 0.000 description 7
• 239000000203 mixture Substances 0.000 description 7
• 239000011541 reaction mixture Substances 0.000 description 7
• 239000007858 starting material Substances 0.000 description 7
• 239000002253 acid Substances 0.000 description 6
• 239000007795 chemical reaction product Substances 0.000 description 6
• 239000003153 chemical reaction reagent Substances 0.000 description 6
• 238000001704 evaporation Methods 0.000 description 6
• 230000007062 hydrolysis Effects 0.000 description 6
• 238000006460 hydrolysis reaction Methods 0.000 description 6
• 238000001953 recrystallisation Methods 0.000 description 6
• RAJWOBJTTGJROA-RNQTWYFASA-N androstane-3,17-dione Chemical class 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 description 5
• 238000009835 boiling Methods 0.000 description 5
• 125000005594 diketone group Chemical group 0.000 description 5
• 238000004821 distillation Methods 0.000 description 5
• 230000008020 evaporation Effects 0.000 description 5
• 125000000468 ketone group Chemical group 0.000 description 5
• 230000007935 neutral effect Effects 0.000 description 5
• 150000001241 acetals Chemical class 0.000 description 4
• 239000003518 caustics Substances 0.000 description 4
• 150000002084 enol ethers Chemical class 0.000 description 4
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
• 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 3
• BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 3
• 239000003638 chemical reducing agent Substances 0.000 description 3
• 238000000605 extraction Methods 0.000 description 3
• 229910052749 magnesium Inorganic materials 0.000 description 3
• 239000011777 magnesium Substances 0.000 description 3
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
• 238000002360 preparation method Methods 0.000 description 3
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
• FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
• AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 2
• RLAHWVDQYNDAGG-UHFFFAOYSA-N Methanetriol Chemical class OC(O)O RLAHWVDQYNDAGG-UHFFFAOYSA-N 0.000 description 2
• LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
• CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
• DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 2
• 150000007513 acids Chemical class 0.000 description 2
• 150000001298 alcohols Chemical class 0.000 description 2
• 229910052782 aluminium Inorganic materials 0.000 description 2
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
• 239000007864 aqueous solution Substances 0.000 description 2
• 230000015572 biosynthetic process Effects 0.000 description 2
• 239000003054 catalyst Substances 0.000 description 2
• 239000007859 condensation product Substances 0.000 description 2
• 238000001816 cooling Methods 0.000 description 2
• 238000000354 decomposition reaction Methods 0.000 description 2
• 238000001035 drying Methods 0.000 description 2
• 125000004494 ethyl ester group Chemical group 0.000 description 2
• 239000000284 extract Substances 0.000 description 2
• 230000004927 fusion Effects 0.000 description 2
• 238000005984 hydrogenation reaction Methods 0.000 description 2
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
• 238000004519 manufacturing process Methods 0.000 description 2
• QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 2
• 238000006386 neutralization reaction Methods 0.000 description 2
• 239000003208 petroleum Substances 0.000 description 2
• 238000005057 refrigeration Methods 0.000 description 2
• DUIOPKIIICUYRZ-UHFFFAOYSA-N semicarbazide Chemical compound NNC(N)=O DUIOPKIIICUYRZ-UHFFFAOYSA-N 0.000 description 2
• 239000000052 vinegar Substances 0.000 description 2
• 235000021419 vinegar Nutrition 0.000 description 2
• 238000005406 washing Methods 0.000 description 2
• 239000008096 xylene Substances 0.000 description 2
• 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 class [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 1
• IBAFAEHLNXQMQA-OFLQVFCSSA-N (8r,9s,10s,13s,14s)-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15-dodecahydro-1h-cyclopenta[a]phenanthrene-3,17-diol Chemical compound C1C(O)CC[C@]2(C)[C@H]3CC[C@](C)(C(=CC4)O)[C@@H]4[C@@H]3CCC21 IBAFAEHLNXQMQA-OFLQVFCSSA-N 0.000 description 1
• HIZVCIIORGCREW-UHFFFAOYSA-N 1,4-dioxene Chemical compound C1COC=CO1 HIZVCIIORGCREW-UHFFFAOYSA-N 0.000 description 1
• NVKAWKQGWWIWPM-ABEVXSGRSA-N 17-β-hydroxy-5-α-Androstan-3-one Chemical compound C1C(=O)CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CC[C@H]21 NVKAWKQGWWIWPM-ABEVXSGRSA-N 0.000 description 1
• FGQLGYBGTRHODR-UHFFFAOYSA-N 2,2-diethoxypropane Chemical compound CCOC(C)(C)OCC FGQLGYBGTRHODR-UHFFFAOYSA-N 0.000 description 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
• QADHLRWLCPCEKT-UHFFFAOYSA-N Androstenediol Natural products C1C(O)CCC2(C)C3CCC(C)(C(CC4)O)C4C3CC=C21 QADHLRWLCPCEKT-UHFFFAOYSA-N 0.000 description 1
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
• IYXGSMUGOJNHAZ-UHFFFAOYSA-N Ethyl malonate Chemical compound CCOC(=O)CC(=O)OCC IYXGSMUGOJNHAZ-UHFFFAOYSA-N 0.000 description 1
• 244000182067 Fraxinus ornus Species 0.000 description 1
• 241001633677 Gagea Species 0.000 description 1
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
• 241000575946 Ione Species 0.000 description 1
• 125000000635 L-ornithyl group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C([H])([H])C([H])([H])C(N([H])[H])([H])[H] 0.000 description 1
• LTXREWYXXSTFRX-QGZVFWFLSA-N Linagliptin Chemical compound N=1C=2N(C)C(=O)N(CC=3N=C4C=CC=CC4=C(C)N=3)C(=O)C=2N(CC#CC)C=1N1CCC[C@@H](N)C1 LTXREWYXXSTFRX-QGZVFWFLSA-N 0.000 description 1
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
• 238000006359 acetalization reaction Methods 0.000 description 1
• NLTQZUCBHQFOIO-UHFFFAOYSA-N acetohydrazide;trimethylazanium;chloride Chemical compound [Cl-].C[NH+](C)C.CC(=O)NN NLTQZUCBHQFOIO-UHFFFAOYSA-N 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
• 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
• 235000019270 ammonium chloride Nutrition 0.000 description 1
• 235000011114 ammonium hydroxide Nutrition 0.000 description 1
• 229960003473 androstanolone Drugs 0.000 description 1
• 229940040526 anhydrous sodium acetate Drugs 0.000 description 1
• 239000006227 byproduct Substances 0.000 description 1
• 244000309466 calf Species 0.000 description 1
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
• 150000001875 compounds Chemical class 0.000 description 1
• 238000005336 cracking Methods 0.000 description 1
• 239000012043 crude product Substances 0.000 description 1
• 230000000694 effects Effects 0.000 description 1
• 150000002148 esters Chemical class 0.000 description 1
• 239000012259 ether extract Substances 0.000 description 1
• 229940035423 ethyl ether Drugs 0.000 description 1
• 210000000720 eyelash Anatomy 0.000 description 1
• 239000003163 gonadal steroid hormone Substances 0.000 description 1
• 238000009499 grossing Methods 0.000 description 1
• 229910052739 hydrogen Inorganic materials 0.000 description 1
• 239000001257 hydrogen Substances 0.000 description 1
• 230000003301 hydrolyzing effect Effects 0.000 description 1
• 150000002500 ions Chemical class 0.000 description 1
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 239000000463 material Substances 0.000 description 1
• 239000000155 melt Substances 0.000 description 1
• 229940095102 methyl benzoate Drugs 0.000 description 1
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 239000012452 mother liquor Substances 0.000 description 1
• LGROKZMEHJZWDU-UHFFFAOYSA-N n-amino-n-phenylnitramide Chemical compound [O-][N+](=O)N(N)C1=CC=CC=C1 LGROKZMEHJZWDU-UHFFFAOYSA-N 0.000 description 1
• 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 230000003287 optical effect Effects 0.000 description 1
• 239000003973 paint Substances 0.000 description 1
• HKOOXMFOFWEVGF-UHFFFAOYSA-N phenylhydrazine Chemical compound NNC1=CC=CC=C1 HKOOXMFOFWEVGF-UHFFFAOYSA-N 0.000 description 1
• 229940067157 phenylhydrazine Drugs 0.000 description 1
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 238000000746 purification Methods 0.000 description 1
• 230000035484 reaction time Effects 0.000 description 1
• 150000003839 salts Chemical class 0.000 description 1
• 229920006395 saturated elastomer Polymers 0.000 description 1
• 239000002904 solvent Substances 0.000 description 1
• 238000003860 storage Methods 0.000 description 1
• 239000000126 substance Substances 0.000 description 1
• 238000004448 titration Methods 0.000 description 1
• 230000009466 transformation Effects 0.000 description 1
• GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
• GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 1
• 238000010626 work up procedure Methods 0.000 description 1