CN106946961A - 一种四烯雌酮的合成方法 - Google Patents
一种四烯雌酮的合成方法 Download PDFInfo
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- CN106946961A CN106946961A CN201710146675.0A CN201710146675A CN106946961A CN 106946961 A CN106946961 A CN 106946961A CN 201710146675 A CN201710146675 A CN 201710146675A CN 106946961 A CN106946961 A CN 106946961A
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- synthetic method
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- alcohol
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- VWAUPFMBXBWEQY-ANULTFPQSA-N Altrenogest Chemical compound C1CC(=O)C=C2CC[C@@H]([C@H]3[C@@](C)([C@](CC3)(O)CC=C)C=C3)C3=C21 VWAUPFMBXBWEQY-ANULTFPQSA-N 0.000 title claims abstract description 41
- 238000010189 synthetic method Methods 0.000 title claims abstract description 17
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims abstract description 15
- 238000006243 chemical reaction Methods 0.000 claims abstract description 15
- 150000001875 compounds Chemical class 0.000 claims abstract description 12
- 239000002904 solvent Substances 0.000 claims abstract description 11
- 238000010792 warming Methods 0.000 claims abstract description 10
- 239000002253 acid Substances 0.000 claims abstract description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims abstract description 7
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims abstract description 6
- 238000001035 drying Methods 0.000 claims abstract description 6
- 230000008014 freezing Effects 0.000 claims abstract description 6
- 238000007710 freezing Methods 0.000 claims abstract description 6
- 238000003756 stirring Methods 0.000 claims abstract description 5
- 238000001953 recrystallisation Methods 0.000 claims abstract description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 15
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 12
- 230000015572 biosynthetic process Effects 0.000 claims description 11
- 150000003431 steroids Chemical class 0.000 claims description 11
- 238000003786 synthesis reaction Methods 0.000 claims description 11
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 6
- 239000011777 magnesium Substances 0.000 claims description 6
- 229910052749 magnesium Inorganic materials 0.000 claims description 6
- 125000000746 allylic group Chemical group 0.000 claims description 5
- 230000031709 bromination Effects 0.000 claims description 5
- 238000005893 bromination reaction Methods 0.000 claims description 5
- 239000007789 gas Substances 0.000 claims description 5
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims description 5
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims description 5
- VYMPLPIFKRHAAC-UHFFFAOYSA-N 1,2-ethanedithiol Chemical compound SCCS VYMPLPIFKRHAAC-UHFFFAOYSA-N 0.000 claims description 2
- ZJLMKPKYJBQJNH-UHFFFAOYSA-N propane-1,3-dithiol Chemical class SCCCS ZJLMKPKYJBQJNH-UHFFFAOYSA-N 0.000 claims description 2
- OSDWBNJEKMUWAV-UHFFFAOYSA-N Allyl chloride Chemical group ClCC=C OSDWBNJEKMUWAV-UHFFFAOYSA-N 0.000 claims 1
- 125000000217 alkyl group Chemical group 0.000 claims 1
- 229920000166 polytrimethylene carbonate Polymers 0.000 claims 1
- YPFDHNVEDLHUCE-UHFFFAOYSA-N propane-1,3-diol Chemical class OCCCO YPFDHNVEDLHUCE-UHFFFAOYSA-N 0.000 claims 1
- 239000002994 raw material Substances 0.000 abstract description 8
- 238000000034 method Methods 0.000 abstract description 5
- 230000001476 alcoholic effect Effects 0.000 abstract 1
- 238000009776 industrial production Methods 0.000 abstract 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 8
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 238000005160 1H NMR spectroscopy Methods 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 5
- 235000011167 hydrochloric acid Nutrition 0.000 description 4
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 241001269238 Data Species 0.000 description 3
- 238000012512 characterization method Methods 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 230000004224 protection Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- DNXHEGUUPJUMQT-CBZIJGRNSA-N Estrone Chemical compound OC1=CC=C2[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 DNXHEGUUPJUMQT-CBZIJGRNSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- 150000002240 furans Chemical class 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000000186 progesterone Substances 0.000 description 2
- 229960003387 progesterone Drugs 0.000 description 2
- DNXHEGUUPJUMQT-UHFFFAOYSA-N (+)-estrone Natural products OC1=CC=C2C3CCC(C)(C(CC4)=O)C4C3CCC2=C1 DNXHEGUUPJUMQT-UHFFFAOYSA-N 0.000 description 1
- 150000000319 19-nortestosterones Chemical class 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- OAGQXMQNOUGMKZ-TZORGIJUSA-N C[C@@]12CCC[C@H]1[C@@H]3CCC4=CCCCC4=C3C(C2)O Chemical compound C[C@@]12CCC[C@H]1[C@@H]3CCC4=CCCCC4=C3C(C2)O OAGQXMQNOUGMKZ-TZORGIJUSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- -1 alkyl diol Chemical class 0.000 description 1
- 229960000971 altrenogest Drugs 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 229960003399 estrone Drugs 0.000 description 1
- 230000012173 estrus Effects 0.000 description 1
- HQVFCQRVQFYGRJ-UHFFFAOYSA-N formic acid;hydrate Chemical compound O.OC=O HQVFCQRVQFYGRJ-UHFFFAOYSA-N 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 230000001072 progestational effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229940050570 regu-mate Drugs 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 238000010025 steaming Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000273 veterinary drug Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
- C07J1/0051—Estrane derivatives
- C07J1/0081—Substituted in position 17 alfa and 17 beta
- C07J1/0088—Substituted in position 17 alfa and 17 beta the substituent in position 17 alfa being an unsaturated hydrocarbon group
- C07J1/0092—Alkenyl derivatives
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Steroid Compounds (AREA)
Abstract
Description
Claims (10)
Priority Applications (1)
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CN201710146675.0A CN106946961B (zh) | 2017-03-13 | 2017-03-13 | 一种四烯雌酮的合成方法 |
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CN201710146675.0A CN106946961B (zh) | 2017-03-13 | 2017-03-13 | 一种四烯雌酮的合成方法 |
Publications (2)
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CN106946961A true CN106946961A (zh) | 2017-07-14 |
CN106946961B CN106946961B (zh) | 2019-08-06 |
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CN201710146675.0A Active CN106946961B (zh) | 2017-03-13 | 2017-03-13 | 一种四烯雌酮的合成方法 |
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Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110407901A (zh) * | 2019-07-04 | 2019-11-05 | 天津市中升挑战生物科技有限公司 | 一种烯丙孕素单晶型物及其制备方法 |
CN110950920A (zh) * | 2019-10-30 | 2020-04-03 | 浙江神洲药业有限公司 | 一种四烯雌酮的制备方法 |
CN113372403A (zh) * | 2020-12-25 | 2021-09-10 | 上海药坦药物研究开发有限公司 | 一种四烯雌酮及其中间体的制备方法 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3573284A (en) * | 1967-09-08 | 1971-03-30 | Roussel Uclaf | Novel delta**4,9,11-gonatrienes |
DD298407A5 (de) * | 1989-09-11 | 1992-02-20 | Jenapharm Gmbh,De | Verfahren zur herstellung von 17alpha-allyl-17beta-hydroxysteroidverbindungen |
CN106397519A (zh) * | 2016-08-30 | 2017-02-15 | 天津市中升挑战生物科技有限公司 | 一种烯丙孕素的制备方法 |
-
2017
- 2017-03-13 CN CN201710146675.0A patent/CN106946961B/zh active Active
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3573284A (en) * | 1967-09-08 | 1971-03-30 | Roussel Uclaf | Novel delta**4,9,11-gonatrienes |
DD298407A5 (de) * | 1989-09-11 | 1992-02-20 | Jenapharm Gmbh,De | Verfahren zur herstellung von 17alpha-allyl-17beta-hydroxysteroidverbindungen |
CN106397519A (zh) * | 2016-08-30 | 2017-02-15 | 天津市中升挑战生物科技有限公司 | 一种烯丙孕素的制备方法 |
Non-Patent Citations (1)
Title |
---|
NARESHKUMAR JAIN ET AL.: "Synthesis and SAR study of novel pseudo-steroids as potent and selective progesterone receptor antagonists", 《BIOORGANIC & MEDICINAL CHEMISTRY LETTERS》 * |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110407901A (zh) * | 2019-07-04 | 2019-11-05 | 天津市中升挑战生物科技有限公司 | 一种烯丙孕素单晶型物及其制备方法 |
CN110950920A (zh) * | 2019-10-30 | 2020-04-03 | 浙江神洲药业有限公司 | 一种四烯雌酮的制备方法 |
CN113372403A (zh) * | 2020-12-25 | 2021-09-10 | 上海药坦药物研究开发有限公司 | 一种四烯雌酮及其中间体的制备方法 |
Also Published As
Publication number | Publication date |
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CN106946961B (zh) | 2019-08-06 |
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PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: A synthetic method of tetraestrone Effective date of registration: 20201225 Granted publication date: 20190806 Pledgee: Xiamen finance Company limited by guarantee Pledgor: XIAMEN OURUIJIE BIOTECHNOLOGY Co.,Ltd. Registration number: Y2020980009948 |
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PC01 | Cancellation of the registration of the contract for pledge of patent right | ||
PC01 | Cancellation of the registration of the contract for pledge of patent right |
Date of cancellation: 20231026 Granted publication date: 20190806 Pledgee: Xiamen finance Company limited by guarantee Pledgor: XIAMEN OURUIJIE BIOTECHNOLOGY CO.,LTD. Registration number: Y2020980009948 |
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PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: A synthesis method of tetraethylestradiol Granted publication date: 20190806 Pledgee: Industrial and Commercial Bank of China Xiamen Xiang'an Branch Pledgor: XIAMEN OURUIJIE BIOTECHNOLOGY CO.,LTD. Registration number: Y2024980000931 |