CN105153258B - The preparation method of 3-beta-hydroxy-androstane-17-ketone - Google Patents
The preparation method of 3-beta-hydroxy-androstane-17-ketone Download PDFInfo
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- CN105153258B CN105153258B CN201510463987.5A CN201510463987A CN105153258B CN 105153258 B CN105153258 B CN 105153258B CN 201510463987 A CN201510463987 A CN 201510463987A CN 105153258 B CN105153258 B CN 105153258B
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- 238000002360 preparation method Methods 0.000 title claims abstract description 25
- 239000003960 organic solvent Substances 0.000 claims abstract description 42
- 238000005984 hydrogenation reaction Methods 0.000 claims abstract description 23
- 238000004128 high performance liquid chromatography Methods 0.000 claims abstract description 14
- 239000002904 solvent Substances 0.000 claims abstract description 13
- 238000000034 method Methods 0.000 claims abstract description 12
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000002994 raw material Substances 0.000 claims abstract description 9
- 238000007171 acid catalysis Methods 0.000 claims abstract description 7
- 238000005903 acid hydrolysis reaction Methods 0.000 claims abstract description 4
- 150000001336 alkenes Chemical class 0.000 claims abstract description 3
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 3
- 238000009903 catalytic hydrogenation reaction Methods 0.000 claims abstract description 3
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 112
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 37
- 238000006243 chemical reaction Methods 0.000 claims description 30
- 239000012065 filter cake Substances 0.000 claims description 23
- 238000005406 washing Methods 0.000 claims description 22
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 20
- 238000003756 stirring Methods 0.000 claims description 17
- 239000012043 crude product Substances 0.000 claims description 16
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 15
- 239000007788 liquid Substances 0.000 claims description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 14
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 claims description 14
- 239000002253 acid Substances 0.000 claims description 13
- 239000000706 filtrate Substances 0.000 claims description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 10
- 239000007787 solid Substances 0.000 claims description 10
- 239000000376 reactant Substances 0.000 claims description 8
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 7
- 238000010792 warming Methods 0.000 claims description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 6
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 6
- 239000003377 acid catalyst Substances 0.000 claims description 6
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 claims description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 5
- 238000003825 pressing Methods 0.000 claims description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 5
- 239000001117 sulphuric acid Substances 0.000 claims description 5
- 235000011149 sulphuric acid Nutrition 0.000 claims description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 4
- 239000000047 product Substances 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 4
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 3
- 239000003054 catalyst Substances 0.000 claims description 3
- 238000001953 recrystallisation Methods 0.000 claims description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 2
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims description 2
- -1 ether Compound Chemical class 0.000 claims description 2
- 235000019253 formic acid Nutrition 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 230000007062 hydrolysis Effects 0.000 claims description 2
- 238000006460 hydrolysis reaction Methods 0.000 claims description 2
- 230000003472 neutralizing effect Effects 0.000 claims description 2
- 235000006408 oxalic acid Nutrition 0.000 claims description 2
- 238000010626 work up procedure Methods 0.000 claims description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 claims 1
- 239000011574 phosphorus Substances 0.000 claims 1
- 229910052698 phosphorus Inorganic materials 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 abstract description 12
- 238000011084 recovery Methods 0.000 abstract description 12
- 150000002576 ketones Chemical class 0.000 abstract description 8
- LFYXIRUBYZVZTH-IHMRHOJGSA-N (5R,8R,9S,10S,13R,14S)-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-15-ol Chemical compound C([C@@H]1CC2)CCC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C(O)CC[C@@]2(C)CC1 LFYXIRUBYZVZTH-IHMRHOJGSA-N 0.000 abstract description 4
- 230000009286 beneficial effect Effects 0.000 abstract description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 abstract description 2
- 230000007613 environmental effect Effects 0.000 abstract description 2
- HFJJFVWDQNSUGH-VMXHOPILSA-N (8s,9s,10r,13s,14s)-10,13-dimethyl-2,7,8,9,11,12,14,15,16,17-decahydro-1h-cyclopenta[a]phenanthrene Chemical compound C1C=C2C=CCC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CCC[C@@]1(C)CC2 HFJJFVWDQNSUGH-VMXHOPILSA-N 0.000 abstract 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 abstract 1
- 150000004678 hydrides Chemical class 0.000 abstract 1
- 238000001035 drying Methods 0.000 description 12
- 229960000583 acetic acid Drugs 0.000 description 9
- 239000003814 drug Substances 0.000 description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 239000000543 intermediate Substances 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 239000008399 tap water Substances 0.000 description 6
- 235000020679 tap water Nutrition 0.000 description 6
- 239000003270 steroid hormone Substances 0.000 description 5
- 238000001914 filtration Methods 0.000 description 4
- 230000000630 rising effect Effects 0.000 description 4
- 241000196324 Embryophyta Species 0.000 description 3
- DWCSNWXARWMZTG-UHFFFAOYSA-N Trigonegenin A Natural products CC1C(C2(CCC3C4(C)CCC(O)C=C4CCC3C2C2)C)C2OC11CCC(C)CO1 DWCSNWXARWMZTG-UHFFFAOYSA-N 0.000 description 3
- 239000003098 androgen Substances 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 230000006837 decompression Effects 0.000 description 3
- 150000001993 dienes Chemical class 0.000 description 3
- WQLVFSAGQJTQCK-VKROHFNGSA-N diosgenin Chemical compound O([C@@H]1[C@@H]([C@]2(CC[C@@H]3[C@@]4(C)CC[C@H](O)CC4=CC[C@H]3[C@@H]2C1)C)[C@@H]1C)[C@]11CC[C@@H](C)CO1 WQLVFSAGQJTQCK-VKROHFNGSA-N 0.000 description 3
- WQLVFSAGQJTQCK-UHFFFAOYSA-N diosgenin Natural products CC1C(C2(CCC3C4(C)CCC(O)CC4=CCC3C2C2)C)C2OC11CCC(C)CO1 WQLVFSAGQJTQCK-UHFFFAOYSA-N 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 239000006260 foam Substances 0.000 description 3
- 239000012362 glacial acetic acid Substances 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 239000012452 mother liquor Substances 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 238000004064 recycling Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 230000008707 rearrangement Effects 0.000 description 2
- OILXMJHPFNGGTO-UHFFFAOYSA-N (22E)-(24xi)-24-methylcholesta-5,22-dien-3beta-ol Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(C)C=CC(C)C(C)C)C1(C)CC2 OILXMJHPFNGGTO-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- OQMZNAMGEHIHNN-UHFFFAOYSA-N 7-Dehydrostigmasterol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)C=CC(CC)C(C)C)CCC33)C)C3=CC=C21 OQMZNAMGEHIHNN-UHFFFAOYSA-N 0.000 description 1
- WYZDXEKUWRCKOB-YDSAWKJFSA-N Mestanolone Chemical compound C([C@@H]1CC2)C(=O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@](C)(O)[C@@]2(C)CC1 WYZDXEKUWRCKOB-YDSAWKJFSA-N 0.000 description 1
- HZYXFRGVBOPPNZ-UHFFFAOYSA-N UNPD88870 Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(C)=CCC(CC)C(C)C)C1(C)CC2 HZYXFRGVBOPPNZ-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 239000003263 anabolic agent Substances 0.000 description 1
- LGJMUZUPVCAVPU-UHFFFAOYSA-N beta-Sitostanol Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(C)CCC(CC)C(C)C)C1(C)CC2 LGJMUZUPVCAVPU-UHFFFAOYSA-N 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 239000003337 fertilizer Substances 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229950008604 mestanolone Drugs 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 239000012450 pharmaceutical intermediate Substances 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 1
- 229960003682 rocuronium bromide Drugs 0.000 description 1
- OYTJKRAYGYRUJK-FMCCZJBLSA-M rocuronium bromide Chemical compound [Br-].N1([C@@H]2[C@@H](O)C[C@@H]3CC[C@H]4[C@@H]5C[C@@H]([C@@H]([C@]5(CC[C@@H]4[C@@]3(C)C2)C)OC(=O)C)[N+]2(CC=C)CCCC2)CCOCC1 OYTJKRAYGYRUJK-FMCCZJBLSA-M 0.000 description 1
- 229930182490 saponin Natural products 0.000 description 1
- 150000007949 saponins Chemical class 0.000 description 1
- 239000010865 sewage Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 238000010025 steaming Methods 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- HCXVJBMSMIARIN-PHZDYDNGSA-N stigmasterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)/C=C/[C@@H](CC)C(C)C)[C@@]1(C)CC2 HCXVJBMSMIARIN-PHZDYDNGSA-N 0.000 description 1
- 229940032091 stigmasterol Drugs 0.000 description 1
- BFDNMXAIBMJLBB-UHFFFAOYSA-N stigmasterol Natural products CCC(C=CC(C)C1CCCC2C3CC=C4CC(O)CCC4(C)C3CCC12C)C(C)C BFDNMXAIBMJLBB-UHFFFAOYSA-N 0.000 description 1
- 235000016831 stigmasterol Nutrition 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 229960004298 vecuronium bromide Drugs 0.000 description 1
- VEPSYABRBFXYIB-PWXDFCLTSA-M vecuronium bromide Chemical compound [Br-].N1([C@@H]2[C@@H](OC(C)=O)C[C@@H]3CC[C@H]4[C@@H]5C[C@@H]([C@@H]([C@]5(CC[C@@H]4[C@@]3(C)C2)C)OC(=O)C)[N+]2(C)CCCCC2)CCCCC1 VEPSYABRBFXYIB-PWXDFCLTSA-M 0.000 description 1
- 239000002351 wastewater Substances 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Steroid Compounds (AREA)
Abstract
The preparation method of 3 β hydroxy-androstane 17 ketone, with 4AD as raw material, in organic solvent, is etherified by 3 alkene of 4AD, makees reagent with triethyl orthoformate, and acid catalysis prepares etherate 3 ethyoxyl androstane 3,5 diene 17 ketone；By this etherate in organic solvent, with palladium/carbon catalytic hydrogenation, obtain intermediate hydrogenation thing 3 ethyoxyl androstane 17 ketone；This hydride acid-catalyzed hydrolysis in the organic solvents such as low-carbon alcohols is obtained 3 β hydroxy-androstane 17 ketone.This product HPLC content more than 99.5%, fusing point 172 ~ 176 degree, synthesize weight total recovery 75 ~ 83%.The inventive method produces 3 β hydroxy-androstane 17 ketone, and raw material is cheap and easy to get, and technological operation is easy, and total yield of products improves 15～20%, production cost low 30～40%.The solvent used in technique, recyclable recycled, both economical, environmental protection again, it is very beneficial to industrialized production.
Description
Technical field
The invention belongs to the fabricating technology of steroid hormone pharmaceutical intermediate, be specifically related to a kind of 3-beta-hydroxy-androstane-17-
The preparation method of ketone.
Background technology
3-beta-hydroxy-androstane-17-ketone is a kind of versatile intermediates producing steroid hormone medicine.With it as raw material, Ke Yisheng
Produce the multiple common class steroid hormone medicine of flaccid muscles such as Rocuronium Bromide, vecuronium bromide；Also mestanolone, rehabilitation can be produced
The multiple common androgen medicines such as dragon.The conventional production methods of 3-beta-hydroxy-androstane-17-ketone, is to carry from Rhizoma Dioscoreae plant
The diosgenin taken, through protection, oxicracking, elimination, it is thus achieved that key intermediate acetic acid gestation diene alcohol ketone (be called for short
Diene) it is raw material, prepare through oximate, rearrangement, acid hydrolysis, hydrogenation, the reaction of basic hydrolysis five step, its process route is shown in attached
Fig. 1.The techniques such as the wherein extraction of diosgenin, oxicracking, the oximate of diene, rearrangement, waste water is more, and is difficult to place
Reason, easily pollutes environment.The more important thing is, along with wild Rhizoma Dioscoreae plant resources is the most exhausted, and artificial growth Rhizoma Dioscoreae plant,
Also because of the rising day by day of the planting costs such as artificial, chemical fertilizer, Saponin is caused, the production cost of diene is doubled and redoubled, and causes 3-
Beta-hydroxy-androstane-17-ketone production cost increases substantially with the market price, already to multiple class steroid hormone medicine of flaccid muscles
Significant impact is created with the world market of androgen medicine.Find new synthetic method, low-cost production 3-beta-hydroxy-
Steroid hormone medicine and the intermediate thereof such as androstane-17-ketone, become the industry task of top priority.Abroad once had document to report, utilize from
The stigmasterol extracted in the residue that soybean oil produces, through modern biotechnology fermentation technique, available synthesizing steroid hormonal medicaments
Another key intermediate 4-AD, is called for short 4AD.Most of androgen and protein anabolic hormone medicine can be produced by 4AD
Thing.But there are no the document report producing 3-beta-hydroxy-androstane-17-ketone with 4AD.
Summary of the invention
It is an object of the invention to provide the preparation method of a kind of new 3-beta-hydroxy-androstane-17-ketone, solve existing technique skill
Many defects such as in art, raw materials for production are expensive, sewage disposal is difficult, complex operation, are greatly reduced 3-beta-hydroxy-androstane-17-
The production cost of ketone.
The technical scheme is that the preparation method of 3-beta-hydroxy-androstane-17-ketone, with 4AD as raw material, organic molten
In agent, being etherified by 3 alkene of 4AD, make reagent with triethyl orthoformate, acid catalysis prepares etherate 3-ethyoxyl-androstane
-3,5-diene-17-ketone；This etherate in organic solvent, with palladium/carbon catalytic hydrogenation, obtain intermediate hydrogenation thing 3-ethyoxyl-
Androstane-17-ketone；This hydrogenation thing acid-catalyzed hydrolysis in organic solvent is obtained 3-beta-hydroxy-androstane-17-ketone.
A, acid catalysis prepare the method for etherate, and by 4AD, in organic solvent and triethyl orthoformate is in acid catalysis
Under, in 20～50 DEG C of stirring reactions 12～16 hours, after having reacted, add 0.02W weak base and be neutralized to pH7～7.5,
Further work-up, obtains etherate 3-ethyoxyl-androstane-3,5 diene-17-ketone, its HPLC content 98.5%～99.5%,
Weight yield about 100～102%；
Described organic solvent includes dichloromethane, toluene, methanol, ethanol；Acid catalyst used include hydrochloric acid, sulphuric acid,
Phosphoric acid, or acetic acid, p-methyl benzenesulfonic acid, oxalic acid；Neutralize weak base used and include inorganic weak bases, organic weak base；Reaction temperature
It it is 20～50 DEG C；Weight proportion between reactant, 4AD: triethyl orthoformate: acid be 1:0.5～1.0:0.01～
0.05, proportioning 4AD between reactant and solvent: organic solvent is 1W:2～8V, wherein W represents g, V representative
ml。
Described organic solvent is ethanol；Acid catalyst is p-methyl benzenesulfonic acid；Neutralizing weak base used is pyridine；Reaction temperature 20～
30℃；Weight proportion between reactant is 1:0.8:0.02；Proportioning between reactant and organic solvent is 1W:2～2.5V,
Or 1W:6～8V, wherein W represents g, V and represents ml.
The preparation of B, intermediate hydrogenation thing, is dissolved in above-mentioned etherate in organic solvent, adds palladium carbon, after displaced air
It is passed through hydrogen, is warming up to 30～60 DEG C and reacts 8～16 hours, emptying after having reacted, filter pressing while hot, wash with solvent,
Filter cake send producer to reclaim, and washing liquid and filtrate merge, and reclaim elutriation after organic solvent, obtain solid；This solid wet product directly with
Ethanol, activated carbon decolorizing recrystallization, must be hydrogenated with thing 3-ethyoxyl-androstane-3,5-diene-17-ketone, HPLC content 99.0% with
On, weight yield 90～95%；
Organic solvent described above includes ethyl acetate, oxolane, acetic acid, acetone, below C4 low-carbon alcohols；Catalysis
Agent includes 5% palladium carbon；Reaction temperature is 30～60 DEG C；Weight proportion between etherate and 5% palladium carbon is 1:0.05～0.25；
Etherate is 1W:4～10V with the proportioning of organic solvent, and wherein W represents g, V and represents ml.
Described organic solvent is ethanol, acetic acid；Catalyst is the palladium carbon of 5%；Reaction temperature 40～45 DEG C, etherate with
The weight proportion of palladium carbon is 1:0.15；Etherate is 1W:8V with the proportioning of organic solvent, and wherein W represents g, V generation
Table ml.
C, the acidification hydrolization of hydrogenation thing, dissolve in organic solvent by above-mentioned hydrogenation thing, add acid catalyst, be warming up to
60～100 DEG C, react 12～18 hours, after having reacted, reclaim organic solvent, elutriation of lowering the temperature, obtain 3-beta-hydroxy-androstane-17-
Ketone crude product；By above-mentioned crude product with ethanol, activated carbon decolorizing recrystallization, obtain 3-beta-hydroxy-androstane-17-ketone, fusing point 129-131
Degree, content ＞ 99%, yield 80-85%；
Above-mentioned organic solvent used includes toluene, formic acid, acetic acid, ethanol, isopropanol, the tert-butyl alcohol；Described acid includes
Hydrochloric acid, hydrobromic acid, perchloric acid, sulphuric acid, or trifluoroacetic acid, p-methyl benzenesulfonic acid etc.；Reaction temperature 60～100 DEG C；Hydrogenation
Thing is 1:0.6～1.2 with the weight proportion of acid；Hydrogenation thing is 1W:4～6V with the weight proportion of organic solvent, wherein W
Represent g, V and represent ml.
Described organic solvent is acetic acid or ethanol；Described acid is hydrochloric acid；Reaction temperature 80～90 DEG C；Hydrogenation thing and sour weight
Proportioning is 1:0.8；Hydrogenation thing is 1W:5V with the proportioning of organic solvent, and wherein W represents g, V and represents ml.
The invention has the beneficial effects as follows: use the present invention to produce preparation 3-beta-hydroxy-androstane-17-ketone, relatively with diosgenin
Making the traditional method of raw material, raw material 4AD wide material sources, synthetic route is economic and environment-friendly, and process conditions are gentle, production operation
Simplicity, good product quality, total yield of products improves 15～20%, production cost low 30～40%.The solvent used in technique,
Recyclable recycled, both economical, environmental protection again, it is very beneficial to industrialized production.
Accompanying drawing explanation
Fig. 1 is the synthetic route chart of conventional production methods 3-beta-hydroxy-androstane-17-ketone.
Fig. 2 is the process route chart that the present invention produces 3 β hydroxy-androstane 17 ketone.
Detailed description of the invention
In order to main points and the spirit of the present invention are described more easily, citing below is explained:
Embodiment one
A, the preparation of etherate
In a 1000ml there-necked flask, add 100g 4AD, 200ml ethanol, 80ml triethyl orthoformate, 2g pair
Toluenesulfonic acid, is incubated in 20-25 DEG C of stirring reaction 12～16 hours, and TLC detects reaction end, after having reacted, adds
3ml pyridine, stirs 20-25 minute and neutralizes acid, then system is cooled to-5～0 DEG C, stirred crystallization 2～3 hours,
Sucking filtration, a small amount of washing with alcohol, washing liquid and filtrate merge, and recycling design and crude product are applied mechanically；Filter cake less than 70 DEG C drying,
Etherate 101.6g, HPLC content 99.2%, weight yield 101.6%.Reaction equation is shown in the Part I of accompanying drawing 2.
B, the preparation of hydrogenation thing
In a 1000ml there-necked flask, add 100g etherate, 800ml ethanol, after dissolving, add the palladium carbon of 15g 5%,
Being warming up to 40-45 DEG C of insulated and stirred react 15～16 hours, TLC detects reaction end, after having reacted, and emptying, while hot
Nitrogen filter pressing, 50ml washing with alcohol, filter cake send producer to reclaim；Washing liquid and filtrate merge, and concentrating under reduced pressure reclaims ethanol set
With.Add 600ml tap water elutriation residual night, filter, obtain solid.Above-mentioned solid is directly added in 800ml ethanol,
Heating makes it dissolve, and adds 5g activated carbon, reflux decolour 1-1.5 hour, filtered while hot, filter cake about 80ml ethanol
Foam washing, merging filtrate and washing liquid, normal pressure is concentrated into recovery about 85% ethanol, is subsequently adding 500ml pure water, continues to steam
The about 150ml solvent containing ethanol 50-60%, then system is cooled to 5-10 DEG C, stirring and crystallizing 2-3 hour, filters, filter
Cake washs with the ethanol solution of a small amount of 50%, and less than 70 DEG C drying must be hydrogenated with thing 94.6g, HPLC content 99.2%, weight
Total recovery 94.6%.Reaction equation is shown in the mid portion of accompanying drawing 2.
The preparation of C, 3-beta-hydroxy-androstane-17-ketone
In a 1000ml there-necked flask, add 100g and be hydrogenated with thing, 500ml ethanol, under stirring at normal temperature, add 80g 30%
Hydrochloric acid, is slowly ramped to 80-84 DEG C, back flow reaction 12-16 hour, after having reacted, and decompression distillation, reclaim about 90-95%
Ethanol, be subsequently adding 600ml tap water, be cooled to 10～15 DEG C, stirring and crystallizing 2-3 hour, filter, be washed to
Neutrality, filter cake less than 70 DEG C drying, obtain 3-beta-hydroxy-androstane-17-ketone crude product.By above-mentioned 3-beta-hydroxy-androstane-17-ketone
Crude product dissolves in 600ml ethanol, adds 5g activated carbon, and temperature rising reflux decolours 1-1.5 hour, filtered while hot, 100ml
Ethanol wash filter cake, washing liquid and filtrate merge, and then the ethanol of normal pressure concentration and recovery about 90% be cooled to-5-0 DEG C, freezing
Crystallize 2-3 hour, filters, a small amount of ethanol wash of filter cake, less than 70 DEG C drying, obtains 3-beta-hydroxy-androstane-17-ketone 84.2g,
Fusing point 173.5-174.0 DEG C, HPLC content 99.7%, yield 84.2%.Disposing mother liquor solvent and crude product are applied mechanically.Reaction equation
See the decline of accompanying drawing 2.
Embodiment two
A, the preparation of etherate
In a 1000ml there-necked flask, add 100g 4AD, 600ml dichloromethane, 80ml triethyl orthoformate,
2g p-methyl benzenesulfonic acid, is incubated in 20-25 degree stirring reaction 12～16 hours, and TLC detects reaction end, after having reacted,
Add 3ml pyridine, stir 20-25 minute and neutralize acid, concentrating under reduced pressure, reclaims dichloromethane, cooling, adds 100ml
Ethanol, is then cooled to-5-0 DEG C by system, stirred crystallization 2～3 hours, sucking filtration, a small amount of washing with alcohol, washing liquid and filter
Liquid merges, and recycling design and crude product are applied mechanically；Filter cake less than 70 DEG C drying, obtains etherate 100.2g, HPLC content 99.4%,
Weight yield 100.2%.
B, the preparation of hydrogenation thing
In a 1000ml there-necked flask, add 100g etherate, 800ml glacial acetic acid, after dissolving, add 15g 5%
Palladium carbon, be warming up to 40-45 degree insulated and stirred react 15～16 hours, TLC detects reaction end, after having reacted, puts
Sky, while hot nitrogen filter pressing, 50ml glacial acetic acid washs, and filter cake send producer to reclaim；Washing liquid and filtrate merge, concentrating under reduced pressure,
Recovery glacial acetic acid is applied mechanically.Add 600ml tap water elutriation residual night, filter, obtain solid.Above-mentioned solid is directly added to 800ml
In ethanol, heating makes it dissolve, and adds 5g activated carbon, reflux decolour 1-1.5 hour, filtered while hot, filter cake about 80ml
Ethanol foam washing, merging filtrate and washing liquid, normal pressure is concentrated into recovery about 85% ethanol, is subsequently adding 500ml pure water, continues
Steam the about 150ml solvent containing ethanol 50-60%, then system is cooled to 5-10 degree, stirring and crystallizing 2-3 hour, filter,
Filter cake washs with the ethanol solution of a small amount of 50%, and less than 70 degree drying must be hydrogenated with thing 92.5g, HPLC content 99.3%,
Weight total recovery 92.5%.
The preparation of C, 3-beta-hydroxy-androstane-17-ketone
In a 1000ml there-necked flask, add 100g and be hydrogenated with thing, 500ml ethanol, under stirring at normal temperature, add 70g 40%
Hydrobromic acid, is slowly ramped to 80-84 DEG C, back flow reaction 12-16 hour, after having reacted, and decompression distillation, reclaim about 90-95%
Ethanol, be subsequently adding 600ml tap water, be cooled to 10～15 DEG C, stirring and crystallizing 2-3 hour, filter, be washed to
Neutrality, filter cake less than 70 DEG C drying, obtain 3-beta-hydroxy-androstane-17-ketone crude product.By above-mentioned 3-beta-hydroxy-androstane-17-ketone
Crude product dissolves in 600ml ethanol, adds 5g activated carbon, and temperature rising reflux decolours 1-1.5 hour, filtered while hot, 100ml
Ethanol wash filter cake, washing liquid and filtrate merge, and then the ethanol of normal pressure concentration and recovery about 90% be cooled to-5-0 degree, cold
Freezeout crystalline substance 2-3 hour, filters, a small amount of ethanol wash of filter cake, less than 70 degree drying, obtains 3-beta-hydroxy-androstane-17-
Ketone 84.2g, fusing point 173.0-173.5 degree, HPLC content 99.7%, yield 84.2%.Disposing mother liquor solvent and crude product set
With.
Embodiment three
A, the preparation of etherate
In a 1000ml there-necked flask, add 100g 4AD, 200ml ethanol, 80ml triethyl orthoformate, 2g 98%
Sulphuric acid, be incubated in 20-25 DEG C stirring reaction 12～16 hours, TLC detect reaction end, after having reacted, addition 3ml
Pyridine, stirs 20-25 minute and neutralizes acid, then system be cooled to-5-0 degree, stirred crystallization 2～3 hours, sucking filtration,
A small amount of washing with alcohol, washing liquid and filtrate merge, and recycling design and crude product are applied mechanically；Filter cake less than 70 DEG C drying, obtains etherate
100.8g, HPLC content 99.0%, weight yield 100.8%.
B, the preparation of hydrogenation thing
In a 1000ml there-necked flask, add 100g etherate, 800ml ethyl acetate, after dissolving, add 15g 5%
Palladium carbon, be warming up to 40-45 DEG C of insulated and stirred and react 15～16 hours, TLC detects reaction end, after having reacted, puts
Sky, while hot nitrogen filter pressing, the washing of 50ml ethyl acetate, filter cake send producer to reclaim；Washing liquid and filtrate merge, concentrating under reduced pressure,
Recovery ethyl acetate is applied mechanically.Add 600ml tap water elutriation residual night, filter, obtain solid.Above-mentioned solid is directly added to
In 800ml ethanol, heating makes it dissolve, and adds 5g activated carbon, reflux decolour 1-1.5 hour, filtered while hot, filter cake
By about 80ml ethanol foam washing, merging filtrate and washing liquid, normal pressure is concentrated into recovery about 85% ethanol, is subsequently adding 500ml pure
Water purification, continues the solvent steaming about 150ml containing ethanol 50-60%, then system is cooled to 5-10 DEG C, stirring and crystallizing 2-3
Hour, filtering, filter cake washs with the ethanol solution of a small amount of 50%, and less than 70 DEG C drying must be hydrogenated with thing 91.6g, HPLC
Content 99.3%, weight total recovery 91.6%.
The preparation of C, 3-beta-hydroxy-androstane-17-ketone
In a 1000ml there-necked flask, add 100g and be hydrogenated with thing, 500ml ethanol, under stirring at normal temperature, add 60g 50%
Perchloric acid, is slowly ramped to 80-84 DEG C, back flow reaction 12-16 hour, after having reacted, and decompression distillation, reclaim about 90-95%
Ethanol, be subsequently adding 600ml tap water, be cooled to 10～15 DEG C, stirring and crystallizing 2-3 hour, filter, be washed to
Neutrality, filter cake less than 70 DEG C drying, obtain 3-beta-hydroxy-androstane-17-ketone crude product.By above-mentioned 3-beta-hydroxy-androstane-17-ketone
Crude product dissolves in 600ml ethanol, adds 5g activated carbon, and temperature rising reflux decolours 1-1.5 hour, filtered while hot, 100ml
Ethanol wash filter cake, washing liquid and filtrate merge, and then the ethanol of normal pressure concentration and recovery about 90% be cooled to-5-0 degree, cold
Freezeout crystalline substance 2-3 hour, filters, a small amount of ethanol wash of filter cake, less than 70 DEG C drying, obtains 3-beta-hydroxy-androstane-17-ketone
84.5g, fusing point 172.5-173.5 DEG C, HPLC content 99.5%, yield 84.5%.Disposing mother liquor solvent and crude product are applied mechanically.
Claims (7)
- The preparation method of 1.3-beta-hydroxy-androstane-17-ketone, it is characterised in that: with 4AD as raw material, in organic solvent, logical Crossing 3 alkene etherificates of 4AD, make reagent with triethyl orthoformate, acid catalysis prepares etherate 3-ethyoxyl-androstane-3,5-diene -17-ketone；This etherate in organic solvent, with palladium carbon catalytic hydrogenation, obtains intermediate hydrogenation thing 3-ethyoxyl-androstane-17- Ketone；This hydrogenation thing acid-catalyzed hydrolysis in organic solvent is obtained 3-beta-hydroxy-androstane-17-ketone.
- The preparation method of 3-beta-hydroxy the most according to claim 1-androstane-17-ketone, is characterized in that, acid catalysis prepares ether The method of compound is, by 4AD, in organic solvent and triethyl orthoformate is under acid catalysis, in 20～50 DEG C of stirrings React 12～16 hours, after having reacted, add 0.02W weak base and be neutralized to pH7～7.5, further work-up, obtain ether Compound 3-ethyoxyl-androstane-3,5 diene-17-ketone, its HPLC content 98.5%～99.5%, weight yield 100～102%； Described organic solvent includes dichloromethane, toluene, methanol, ethanol；Acid catalyst used includes hydrochloric acid, sulphuric acid, phosphorus Acid, or acetic acid, p-methyl benzenesulfonic acid, oxalic acid；Neutralize weak base used and include inorganic weak bases, organic weak base；Reaction temperature is 20～50 DEG C；Weight proportion between reactant, 4AD: triethyl orthoformate: acid be 1: 0.5～1.0: 0.01～ 0.05, proportioning 4AD between reactant and solvent: organic solvent is 1W: 2～8V, wherein W represents g, V representative ml。
- The preparation method of 3-beta-hydroxy the most according to claim 2-androstane-17-ketone, is characterized in that, described organic solvent For ethanol；Acid catalyst is p-methyl benzenesulfonic acid；Neutralizing weak base used is pyridine；Reaction temperature 20～30 DEG C；Between reactant Weight proportion be 1: 0.8: 0.02；Proportioning between reactant and solvent, 4AD: organic solvent is 1W: 2～2.5V, Or 1W: 6～8V.
- The preparation method of 3-beta-hydroxy the most according to claim 1-androstane-17-ketone, is characterized in that, intermediate hydrogenation thing Preparation, above-mentioned etherate is dissolved in organic solvent, add palladium carbon, be passed through hydrogen after displaced air, be warming up to 30～ 60 DEG C are reacted 8～16 hours, emptying after having reacted, and filter pressing while hot is washed with solvent, and filter cake send producer to reclaim, washing liquid Merge with filtrate, reclaim elutriation after organic solvent, obtain solid；This solid wet product is directly heavily tied with ethanol, activated carbon decolorizing Crystalline substance, must be hydrogenated with thing 3-ethyoxyl-androstane-3,5-diene-17-ketone, HPLC content more than 99.0%, weight yield 90～95%； Organic solvent described above includes ethyl acetate, oxolane, acetic acid, acetone, below C4 low-carbon alcohols；Catalyst includes 5% palladium carbon；Reaction temperature is 30～60 DEG C；Weight proportion between etherate and 5% palladium carbon is 1: 0.05～0.25；Etherificate Thing is 1W: 4～10V with the proportioning of organic solvent, and wherein W represents g, V and represents ml.
- The preparation method of 3-beta-hydroxy the most according to claim 4-androstane-17-ketone, is characterized in that, described organic solvent It is ethanol, acetic acid；Catalyst is the palladium carbon of 5%；Reaction temperature 40～45 DEG C, etherate with the weight proportion of palladium carbon is 1∶0.15；Etherate is 1W with the proportioning of organic solvent: 8V, wherein W represents g, V and represents ml.
- The preparation method of 3-beta-hydroxy the most according to claim 1-androstane-17-ketone, is characterized in that, the acidifying of hydrogenation thing Hydrolysis, dissolves in organic solvent by above-mentioned hydrogenation thing, adds acid catalyst, is warming up to 60～100 DEG C, and reaction 12～18 is little Time, after having reacted, reclaim organic solvent, elutriation of lowering the temperature, obtain 3-beta-hydroxy-androstane-17-ketone crude product；By above-mentioned crude product with Ethanol, activated carbon decolorizing recrystallization, obtain 3-beta-hydroxy-androstane-17-ketone, fusing point 129-131 degree, content ＞ 99%, receive Rate 80-85%；Above-mentioned organic solvent used includes toluene, formic acid, acetic acid, ethanol, isopropanol, the tert-butyl alcohol；Described Acid includes hydrochloric acid, hydrobromic acid, perchloric acid, sulphuric acid, or trifluoroacetic acid, p-methyl benzenesulfonic acid；Reaction temperature 60～100 DEG C； Hydrogenation thing is 1: 0.6～1.2 with the weight proportion of acid；Hydrogenation thing is 1W: 4～6V with the weight proportion of organic solvent, its Middle W represents g, V and represents ml.
- The preparation method of 3-beta-hydroxy the most according to claim 6-androstane-17-ketone, is characterized in that, described organic solvent It is acetic acid or ethanol；Described acid is hydrochloric acid；Reaction temperature 80～90 DEG C；Hydrogenation thing is 1: 0.8 with the weight proportion of acid； Hydrogenation thing is 1W with the proportioning of organic solvent: 5V, wherein W represents g, V and represents ml.
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| Title |
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| "Selective hydrogenation of α,β-unsaturated oxosteroids with homogeneous rhodium catalysts";Rui M.D. Nunes et al.;《Journal of Molecular Catalysis A: Chemical》;20060118;第247卷;275-282 * |
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