CN1563003A - Suitable industrialized method of preparing Lamivudine - Google Patents
Suitable industrialized method of preparing Lamivudine Download PDFInfo
- Publication number
- CN1563003A CN1563003A CN 200410023744 CN200410023744A CN1563003A CN 1563003 A CN1563003 A CN 1563003A CN 200410023744 CN200410023744 CN 200410023744 CN 200410023744 A CN200410023744 A CN 200410023744A CN 1563003 A CN1563003 A CN 1563003A
- Authority
- CN
- China
- Prior art keywords
- oxathiolane
- menthyl ester
- carboxylic acid
- acid
- hydroxyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- JTEGQNOMFQHVDC-NKWVEPMBSA-N lamivudine Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)SC1 JTEGQNOMFQHVDC-NKWVEPMBSA-N 0.000 title claims description 17
- 229960001627 lamivudine Drugs 0.000 title claims description 17
- 238000000034 method Methods 0.000 title abstract description 8
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 claims abstract description 44
- HHLFWLYXYJOTON-UHFFFAOYSA-N glyoxylic acid Chemical compound OC(=O)C=O HHLFWLYXYJOTON-UHFFFAOYSA-N 0.000 claims abstract description 24
- 229940104302 cytosine Drugs 0.000 claims abstract description 19
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 claims abstract description 14
- -1 menthol ester Chemical class 0.000 claims abstract description 14
- 229940041616 menthol Drugs 0.000 claims abstract description 13
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 claims abstract description 10
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 7
- 230000002829 reductive effect Effects 0.000 claims abstract description 6
- 239000002904 solvent Substances 0.000 claims abstract description 5
- 239000003054 catalyst Substances 0.000 claims abstract description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 3
- 150000002148 esters Chemical class 0.000 claims description 52
- 238000002360 preparation method Methods 0.000 claims description 16
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
- CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 claims description 8
- 229960003328 benzoyl peroxide Drugs 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 238000009833 condensation Methods 0.000 claims description 4
- 230000005494 condensation Effects 0.000 claims description 4
- 238000002425 crystallisation Methods 0.000 claims description 4
- 230000008025 crystallization Effects 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- LOWHAEXKCMFUMV-UHFFFAOYSA-N 5-hydroxy-1,3-oxathiolane-2-carboxylic acid Chemical compound OC1CSC(C(O)=O)O1 LOWHAEXKCMFUMV-UHFFFAOYSA-N 0.000 claims description 3
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical group C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 claims description 2
- 238000005917 acylation reaction Methods 0.000 claims description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 2
- 229910052782 aluminium Inorganic materials 0.000 claims description 2
- 239000004411 aluminium Substances 0.000 claims description 2
- 239000011968 lewis acid catalyst Substances 0.000 claims description 2
- 238000007670 refining Methods 0.000 claims description 2
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 claims 1
- 229910000077 silane Inorganic materials 0.000 claims 1
- 239000002994 raw material Substances 0.000 abstract description 5
- 239000003638 chemical reducing agent Substances 0.000 abstract 1
- 239000007787 solid Substances 0.000 description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- 239000000243 solution Substances 0.000 description 14
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 10
- 238000003756 stirring Methods 0.000 description 7
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- SFLGIMGLWCVAHP-UHFFFAOYSA-N 5h-oxathiole Chemical compound C1OSC=C1 SFLGIMGLWCVAHP-UHFFFAOYSA-N 0.000 description 5
- 230000008014 freezing Effects 0.000 description 5
- 238000007710 freezing Methods 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- PFTIVKCRALCOLB-UHFFFAOYSA-N [SiH4].[N] Chemical compound [SiH4].[N] PFTIVKCRALCOLB-UHFFFAOYSA-N 0.000 description 3
- 238000004090 dissolution Methods 0.000 description 3
- 238000005194 fractionation Methods 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 238000013019 agitation Methods 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000002777 nucleoside Substances 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 229960001866 silicon dioxide Drugs 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Natural products CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 description 1
- 125000001755 (-)-menthol group Chemical group 0.000 description 1
- FFRBMBIXVSCUFS-UHFFFAOYSA-N 2,4-dinitro-1-naphthol Chemical compound C1=CC=C2C(O)=C([N+]([O-])=O)C=C([N+]([O-])=O)C2=C1 FFRBMBIXVSCUFS-UHFFFAOYSA-N 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 241000534944 Thia Species 0.000 description 1
- ILYXXUBAZBRPLA-UHFFFAOYSA-N [O-]C([S+]1OCCC1)=O Chemical compound [O-]C([S+]1OCCC1)=O ILYXXUBAZBRPLA-UHFFFAOYSA-N 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000003317 industrial substance Substances 0.000 description 1
- 229960004873 levomenthol Drugs 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 1
- 229940127073 nucleoside analogue Drugs 0.000 description 1
- 125000003835 nucleoside group Chemical group 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 235000002639 sodium chloride Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- MNESLHFFAVMPAT-UHFFFAOYSA-N trifluoromethanesulfonate;trimethylazanium Chemical compound C[NH+](C)C.[O-]S(=O)(=O)C(F)(F)F MNESLHFFAVMPAT-UHFFFAOYSA-N 0.000 description 1
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- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Claims (5)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN 200410023744 CN1274686C (en) | 2004-03-17 | 2004-03-17 | Suitable industrialized method of preparing Lamivudine |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN 200410023744 CN1274686C (en) | 2004-03-17 | 2004-03-17 | Suitable industrialized method of preparing Lamivudine |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1563003A true CN1563003A (en) | 2005-01-12 |
CN1274686C CN1274686C (en) | 2006-09-13 |
Family
ID=34480293
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN 200410023744 Expired - Lifetime CN1274686C (en) | 2004-03-17 | 2004-03-17 | Suitable industrialized method of preparing Lamivudine |
Country Status (1)
Country | Link |
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CN (1) | CN1274686C (en) |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN100360528C (en) * | 2005-08-31 | 2008-01-09 | 四川大学 | Preparation of 4-amino-1-(2-methylol-1,3-oxapentane-5-group)-2(1H)-pyrimidone |
CN102234269A (en) * | 2010-04-29 | 2011-11-09 | 重庆医药工业研究院有限责任公司 | Industrial preparation method for lamivudine |
CN102796088A (en) * | 2012-05-21 | 2012-11-28 | 湖南千金湘江药业股份有限公司 | Method for preparing lamivudine |
CN102796089A (en) * | 2012-08-16 | 2012-11-28 | 江苏科本医药化学有限公司 | Preparation method of lamivudine intermediate and lamivudine |
CN103864835A (en) * | 2013-03-26 | 2014-06-18 | 安徽贝克联合制药有限公司 | Preparation method for improving stereoselectivity of lamivudine intermediate |
CN109311862A (en) * | 2016-06-14 | 2019-02-05 | 纳尔逊曼德拉城市大学 | The manufacturing method of Lamivudine and emtricitabine |
CN110437216A (en) * | 2019-08-21 | 2019-11-12 | 武汉工程大学 | A kind of synthetic method of Lamivudine |
CN111253215A (en) * | 2018-11-30 | 2020-06-09 | 上海科胜药物研发有限公司 | L-menthol recovery process method |
-
2004
- 2004-03-17 CN CN 200410023744 patent/CN1274686C/en not_active Expired - Lifetime
Cited By (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN100360528C (en) * | 2005-08-31 | 2008-01-09 | 四川大学 | Preparation of 4-amino-1-(2-methylol-1,3-oxapentane-5-group)-2(1H)-pyrimidone |
CN102234269A (en) * | 2010-04-29 | 2011-11-09 | 重庆医药工业研究院有限责任公司 | Industrial preparation method for lamivudine |
CN102234269B (en) * | 2010-04-29 | 2015-09-16 | 重庆医药工业研究院有限责任公司 | The industrialized process for preparing of lamivudine |
CN102796088A (en) * | 2012-05-21 | 2012-11-28 | 湖南千金湘江药业股份有限公司 | Method for preparing lamivudine |
CN102796089A (en) * | 2012-08-16 | 2012-11-28 | 江苏科本医药化学有限公司 | Preparation method of lamivudine intermediate and lamivudine |
CN102796089B (en) * | 2012-08-16 | 2015-06-17 | 江苏科本医药化学有限公司 | Preparation method of lamivudine intermediate and lamivudine |
CN103864835A (en) * | 2013-03-26 | 2014-06-18 | 安徽贝克联合制药有限公司 | Preparation method for improving stereoselectivity of lamivudine intermediate |
CN109311862A (en) * | 2016-06-14 | 2019-02-05 | 纳尔逊曼德拉城市大学 | The manufacturing method of Lamivudine and emtricitabine |
CN111253215A (en) * | 2018-11-30 | 2020-06-09 | 上海科胜药物研发有限公司 | L-menthol recovery process method |
CN111253215B (en) * | 2018-11-30 | 2023-04-11 | 上海科胜药物研发有限公司 | L-menthol recovery process method |
CN110437216A (en) * | 2019-08-21 | 2019-11-12 | 武汉工程大学 | A kind of synthetic method of Lamivudine |
CN110437216B (en) * | 2019-08-21 | 2023-04-11 | 武汉工程大学 | Synthetic method of lamivudine |
Also Published As
Publication number | Publication date |
---|---|
CN1274686C (en) | 2006-09-13 |
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Owner name: SHANDONG WEIFANG PHARMACEUTICAL FACTORY CO., LTD. Free format text: FORMER OWNER: JIUCHUANG CHEMICAL CO., LTD., JINAN Effective date: 20120606 |
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Free format text: CORRECT: ADDRESS; FROM: 250100 JINAN, SHANDONG PROVINCE TO: 251021 WEIFANG, SHANDONG PROVINCE |
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Effective date of registration: 20120606 Address after: 251021 No. 1 West Palace Street, Weicheng District, Shandong, Weifang Patentee after: SHANDONG WEIFANG PHARMACEUTICAL FACTORY Co.,Ltd. Address before: 250100 A, Pioneer Park, Huayang Road, Licheng District, Shandong, Ji'nan 417 Patentee before: Jinan Inovas Chemical Co.,Ltd. |
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C56 | Change in the name or address of the patentee | ||
CP02 | Change in the address of a patent holder |
Address after: Yu Shandong city in Weifang Province, 251021 North Street Hanting District No. 2709 Patentee after: SHANDONG WEIFANG PHARMACEUTICAL FACTORY Co.,Ltd. Address before: 251021 No. 1 West Palace Street, Weicheng District, Shandong, Weifang Patentee before: SHANDONG WEIFANG PHARMACEUTICAL FACTORY Co.,Ltd. |
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C56 | Change in the name or address of the patentee | ||
CP03 | Change of name, title or address |
Address after: Yu Shandong city in Weifang Province, 261100 North Street Hanting District No. 2709 Patentee after: Zhongfu industry Limited by Share Ltd. Address before: Yu Shandong city in Weifang Province, 251021 North Street Hanting District No. 2709 Patentee before: SHANDONG WEIFANG PHARMACEUTICAL FACTORY Co.,Ltd. |
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CX01 | Expiry of patent term |
Granted publication date: 20060913 |
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CX01 | Expiry of patent term |