CN112745371A - 一种伊维菌素的制备方法 - Google Patents
一种伊维菌素的制备方法 Download PDFInfo
- Publication number
- CN112745371A CN112745371A CN202011359842.8A CN202011359842A CN112745371A CN 112745371 A CN112745371 A CN 112745371A CN 202011359842 A CN202011359842 A CN 202011359842A CN 112745371 A CN112745371 A CN 112745371A
- Authority
- CN
- China
- Prior art keywords
- reaction
- abamectin
- ivermectin
- catalyst
- raw material
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Links
- AZSNMRSAGSSBNP-UHFFFAOYSA-N 22,23-dihydroavermectin B1a Natural products C1CC(C)C(C(C)CC)OC21OC(CC=C(C)C(OC1OC(C)C(OC3OC(C)C(O)C(OC)C3)C(OC)C1)C(C)C=CC=C1C3(C(C(=O)O4)C=C(C)C(O)C3OC1)O)CC4C2 AZSNMRSAGSSBNP-UHFFFAOYSA-N 0.000 title claims abstract description 23
- SPBDXSGPUHCETR-JFUDTMANSA-N 8883yp2r6d Chemical compound O1[C@@H](C)[C@H](O)[C@@H](OC)C[C@@H]1O[C@@H]1[C@@H](OC)C[C@H](O[C@@H]2C(=C/C[C@@H]3C[C@@H](C[C@@]4(O[C@@H]([C@@H](C)CC4)C(C)C)O3)OC(=O)[C@@H]3C=C(C)[C@@H](O)[C@H]4OC\C([C@@]34O)=C/C=C/[C@@H]2C)/C)O[C@H]1C.C1C[C@H](C)[C@@H]([C@@H](C)CC)O[C@@]21O[C@H](C\C=C(C)\[C@@H](O[C@@H]1O[C@@H](C)[C@H](O[C@@H]3O[C@@H](C)[C@H](O)[C@@H](OC)C3)[C@@H](OC)C1)[C@@H](C)\C=C\C=C/1[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\1)O)C[C@H]4C2 SPBDXSGPUHCETR-JFUDTMANSA-N 0.000 title claims abstract description 23
- 229960002418 ivermectin Drugs 0.000 title claims abstract description 23
- 238000002360 preparation method Methods 0.000 title claims abstract description 7
- 238000006243 chemical reaction Methods 0.000 claims abstract description 91
- 239000005660 Abamectin Substances 0.000 claims abstract description 39
- 239000000463 material Substances 0.000 claims abstract description 38
- IBSREHMXUMOFBB-JFUDTMANSA-N 5u8924t11h Chemical compound O1[C@@H](C)[C@H](O)[C@@H](OC)C[C@@H]1O[C@@H]1[C@@H](OC)C[C@H](O[C@@H]2C(=C/C[C@@H]3C[C@@H](C[C@@]4(O3)C=C[C@H](C)[C@@H](C(C)C)O4)OC(=O)[C@@H]3C=C(C)[C@@H](O)[C@H]4OC\C([C@@]34O)=C/C=C/[C@@H]2C)/C)O[C@H]1C.C1=C[C@H](C)[C@@H]([C@@H](C)CC)O[C@]11O[C@H](C\C=C(C)\[C@@H](O[C@@H]2O[C@@H](C)[C@H](O[C@@H]3O[C@@H](C)[C@H](O)[C@@H](OC)C3)[C@@H](OC)C2)[C@@H](C)\C=C\C=C/2[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\2)O)C[C@H]4C1 IBSREHMXUMOFBB-JFUDTMANSA-N 0.000 claims abstract description 36
- 229950008167 abamectin Drugs 0.000 claims abstract description 36
- 238000000034 method Methods 0.000 claims abstract description 25
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 20
- 239000003054 catalyst Substances 0.000 claims abstract description 20
- 239000001257 hydrogen Substances 0.000 claims abstract description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 14
- 239000003960 organic solvent Substances 0.000 claims abstract description 7
- 238000002156 mixing Methods 0.000 claims abstract description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 30
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical group CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 20
- 229910052757 nitrogen Inorganic materials 0.000 claims description 15
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims description 10
- 239000000706 filtrate Substances 0.000 claims description 9
- 239000012043 crude product Substances 0.000 claims description 8
- 238000001914 filtration Methods 0.000 claims description 8
- WWGXHTXOZKVJDN-UHFFFAOYSA-M sodium;n,n-diethylcarbamodithioate;trihydrate Chemical compound O.O.O.[Na+].CCN(CC)C([S-])=S WWGXHTXOZKVJDN-UHFFFAOYSA-M 0.000 claims description 8
- 238000003756 stirring Methods 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- 239000008213 purified water Substances 0.000 claims description 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 5
- 238000001035 drying Methods 0.000 claims description 4
- 239000012065 filter cake Substances 0.000 claims description 4
- 239000007787 solid Substances 0.000 claims description 4
- 238000010438 heat treatment Methods 0.000 claims description 2
- 238000012805 post-processing Methods 0.000 claims description 2
- 239000006227 byproduct Substances 0.000 abstract description 22
- 239000000047 product Substances 0.000 abstract description 22
- 238000004440 column chromatography Methods 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 description 42
- 239000000243 solution Substances 0.000 description 32
- 239000012295 chemical reaction liquid Substances 0.000 description 28
- 238000001816 cooling Methods 0.000 description 15
- 239000002904 solvent Substances 0.000 description 14
- 239000007788 liquid Substances 0.000 description 13
- 238000010606 normalization Methods 0.000 description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 11
- 239000000203 mixture Substances 0.000 description 11
- 238000010626 work up procedure Methods 0.000 description 6
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 4
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 238000005984 hydrogenation reaction Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 230000000749 insecticidal effect Effects 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- 244000045947 parasite Species 0.000 description 2
- 238000005086 pumping Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 230000001502 supplementing effect Effects 0.000 description 2
- 238000001291 vacuum drying Methods 0.000 description 2
- 241000238421 Arthropoda Species 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000244206 Nematoda Species 0.000 description 1
- 241001468227 Streptomyces avermitilis Species 0.000 description 1
- 239000000642 acaricide Substances 0.000 description 1
- 238000012271 agricultural production Methods 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- RRZXIRBKKLTSOM-XPNPUAGNSA-N avermectin B1a Chemical compound C1=C[C@H](C)[C@@H]([C@@H](C)CC)O[C@]11O[C@H](C\C=C(C)\[C@@H](O[C@@H]2O[C@@H](C)[C@H](O[C@@H]3O[C@@H](C)[C@H](O)[C@@H](OC)C3)[C@@H](OC)C2)[C@@H](C)\C=C\C=C/2[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\2)O)C[C@H]4C1 RRZXIRBKKLTSOM-XPNPUAGNSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000002917 insecticide Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000003120 macrolide antibiotic agent Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000007830 nerve conduction Effects 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 238000011112 process operation Methods 0.000 description 1
- QBERHIJABFXGRZ-UHFFFAOYSA-M rhodium;triphenylphosphane;chloride Chemical compound [Cl-].[Rh].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 QBERHIJABFXGRZ-UHFFFAOYSA-M 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- FEQPHYCEZKWPNE-UHFFFAOYSA-K trichlororhodium;triphenylphosphane Chemical compound Cl[Rh](Cl)Cl.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 FEQPHYCEZKWPNE-UHFFFAOYSA-K 0.000 description 1
- 239000011995 wilkinson's catalyst Substances 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
- C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms
- C07H17/08—Hetero rings containing eight or more ring members, e.g. erythromycins
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/0093—Microreactors, e.g. miniaturised or microfabricated reactors
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
原料/% | 产物/% | 杂质/%(RRT=1.3-1.5) | |
反应液 | 4.06 | 90.70 | 2.37 |
成品 | 0.25 | 96.12 | 2.03 |
Claims (10)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
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CN202011359842.8A CN112745371A (zh) | 2020-11-27 | 2020-11-27 | 一种伊维菌素的制备方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
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CN202011359842.8A CN112745371A (zh) | 2020-11-27 | 2020-11-27 | 一种伊维菌素的制备方法 |
Publications (1)
Publication Number | Publication Date |
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CN112745371A true CN112745371A (zh) | 2021-05-04 |
Family
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CN202011359842.8A Pending CN112745371A (zh) | 2020-11-27 | 2020-11-27 | 一种伊维菌素的制备方法 |
Country Status (1)
Country | Link |
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CN (1) | CN112745371A (zh) |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101362786A (zh) * | 2008-10-06 | 2009-02-11 | 山东齐发药业有限公司 | 一种伊维菌素的制备方法 |
CN103333290A (zh) * | 2013-07-23 | 2013-10-02 | 蒲城瑞鹰新材料科技有限公司 | 一种氢化丁腈橡胶的微通道反应器连续生产工艺 |
-
2020
- 2020-11-27 CN CN202011359842.8A patent/CN112745371A/zh active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101362786A (zh) * | 2008-10-06 | 2009-02-11 | 山东齐发药业有限公司 | 一种伊维菌素的制备方法 |
CN103333290A (zh) * | 2013-07-23 | 2013-10-02 | 蒲城瑞鹰新材料科技有限公司 | 一种氢化丁腈橡胶的微通道反应器连续生产工艺 |
Non-Patent Citations (1)
Title |
---|
何伟等: ""微反应器在合成化学中的应用"", 《应用化学》 * |
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PB01 | Publication | ||
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CB02 | Change of applicant information |
Address after: 310011 floor 3, building 94, No. 700, Shixiang Road, Gongshu District, Hangzhou City, Zhejiang Province Applicant after: Zhejiang Hunda Biotechnology Co.,Ltd. Applicant after: HANGZHOU ZHONGMEI HUADONG PHARMACEUTICAL Co.,Ltd. Address before: 310000 room d2014-2017, building 2, 452, 6 Baiyang street, Qiantang New District, Hangzhou City, Zhejiang Province Applicant before: Zhejiang Hunda Biotechnology Co.,Ltd. Applicant before: HANGZHOU ZHONGMEI HUADONG PHARMACEUTICAL Co.,Ltd. |
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CB02 | Change of applicant information | ||
RJ01 | Rejection of invention patent application after publication |
Application publication date: 20210504 |
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RJ01 | Rejection of invention patent application after publication |