CN101514167A - 手性巴氯芬的制备方法 - Google Patents
手性巴氯芬的制备方法 Download PDFInfo
- Publication number
- CN101514167A CN101514167A CNA200910080236XA CN200910080236A CN101514167A CN 101514167 A CN101514167 A CN 101514167A CN A200910080236X A CNA200910080236X A CN A200910080236XA CN 200910080236 A CN200910080236 A CN 200910080236A CN 101514167 A CN101514167 A CN 101514167A
- Authority
- CN
- China
- Prior art keywords
- preparation
- phenyl
- chloro
- reaction
- baclofen
- 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
- KPYSYYIEGFHWSV-UHFFFAOYSA-N Baclofen Chemical compound OC(=O)CC(CN)C1=CC=C(Cl)C=C1 KPYSYYIEGFHWSV-UHFFFAOYSA-N 0.000 title claims abstract description 13
- 229960000794 baclofen Drugs 0.000 title claims abstract description 13
- 238000000034 method Methods 0.000 title claims abstract description 9
- 238000006243 chemical reaction Methods 0.000 claims abstract description 21
- 239000003054 catalyst Substances 0.000 claims abstract description 10
- 238000006462 rearrangement reaction Methods 0.000 claims abstract description 8
- 238000002360 preparation method Methods 0.000 claims description 22
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 19
- KPYSYYIEGFHWSV-QMMMGPOBSA-N Arbaclofen Chemical compound OC(=O)C[C@@H](CN)C1=CC=C(Cl)C=C1 KPYSYYIEGFHWSV-QMMMGPOBSA-N 0.000 claims description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 14
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 13
- -1 isopropyl ester Chemical class 0.000 claims description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 13
- KPYSYYIEGFHWSV-MRVPVSSYSA-N (3s)-4-amino-3-(4-chlorophenyl)butanoic acid Chemical compound OC(=O)C[C@H](CN)C1=CC=C(Cl)C=C1 KPYSYYIEGFHWSV-MRVPVSSYSA-N 0.000 claims description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- 230000032050 esterification Effects 0.000 claims description 9
- 238000005886 esterification reaction Methods 0.000 claims description 9
- VANNPISTIUFMLH-UHFFFAOYSA-N glutaric anhydride Chemical compound O=C1CCCC(=O)O1 VANNPISTIUFMLH-UHFFFAOYSA-N 0.000 claims description 9
- 229910021529 ammonia Inorganic materials 0.000 claims description 7
- 239000007810 chemical reaction solvent Substances 0.000 claims description 7
- 238000007142 ring opening reaction Methods 0.000 claims description 7
- 101000924984 Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720) 3-dehydroquinate dehydratase Proteins 0.000 claims description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 6
- LJOQGZACKSYWCH-UHFFFAOYSA-N dihydro quinine Natural products C1=C(OC)C=C2C(C(O)C3CC4CCN3CC4CC)=CC=NC2=C1 LJOQGZACKSYWCH-UHFFFAOYSA-N 0.000 claims description 6
- URXVLIVRJJNJII-UHFFFAOYSA-N 3-(4-chlorophenyl)pentanedioic acid Chemical compound OC(=O)CC(CC(O)=O)C1=CC=C(Cl)C=C1 URXVLIVRJJNJII-UHFFFAOYSA-N 0.000 claims description 5
- QOSMNYMQXIVWKY-UHFFFAOYSA-N Propyl levulinate Chemical compound CCCOC(=O)CCC(C)=O QOSMNYMQXIVWKY-UHFFFAOYSA-N 0.000 claims description 5
- 125000004494 ethyl ester group Chemical group 0.000 claims description 5
- 150000004702 methyl esters Chemical class 0.000 claims description 5
- LJOQGZACKSYWCH-LHHVKLHASA-N (s)-[(2r,4s,5r)-5-ethyl-1-azabicyclo[2.2.2]octan-2-yl]-(6-methoxyquinolin-4-yl)methanol Chemical class C1=C(OC)C=C2C([C@H](O)[C@H]3C[C@@H]4CCN3C[C@@H]4CC)=CC=NC2=C1 LJOQGZACKSYWCH-LHHVKLHASA-N 0.000 claims description 4
- 230000035484 reaction time Effects 0.000 claims description 4
- 239000003153 chemical reaction reagent Substances 0.000 claims description 3
- JMQGGPRJQOQKRT-UHFFFAOYSA-N diphenyl hydrogen phosphate;azide Chemical compound [N-]=[N+]=[N-].C=1C=CC=CC=1OP(=O)(O)OC1=CC=CC=C1 JMQGGPRJQOQKRT-UHFFFAOYSA-N 0.000 claims description 3
- 230000000694 effects Effects 0.000 claims description 3
- SNHMUERNLJLMHN-UHFFFAOYSA-N iodobenzene Chemical class IC1=CC=CC=C1 SNHMUERNLJLMHN-UHFFFAOYSA-N 0.000 claims description 3
- 230000008569 process Effects 0.000 claims description 3
- SNOFKGQEUYMNCE-UHFFFAOYSA-N 2,2,2-trifluoro-1-$l^{1}-oxidanylethanone Chemical compound [O]C(=O)C(F)(F)F SNOFKGQEUYMNCE-UHFFFAOYSA-N 0.000 claims description 2
- 235000011114 ammonium hydroxide Nutrition 0.000 claims description 2
- 238000005915 ammonolysis reaction Methods 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 239000012153 distilled water Substances 0.000 claims description 2
- 230000007062 hydrolysis Effects 0.000 claims description 2
- 238000006460 hydrolysis reaction Methods 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 238000004064 recycling Methods 0.000 claims description 2
- 230000015572 biosynthetic process Effects 0.000 abstract description 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 2
- OCZRLOJECISNAO-UHFFFAOYSA-N 4-(4-chlorophenyl)oxane-2,6-dione Chemical compound C1=CC(Cl)=CC=C1C1CC(=O)OC(=O)C1 OCZRLOJECISNAO-UHFFFAOYSA-N 0.000 abstract 2
- JFCQEDHGNNZCLN-UHFFFAOYSA-N glutaric acid Chemical compound OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 abstract 2
- 150000001875 compounds Chemical class 0.000 abstract 1
- 239000007858 starting material Substances 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- 238000005481 NMR spectroscopy Methods 0.000 description 8
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 5
- 238000001035 drying Methods 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 239000012141 concentrate Substances 0.000 description 3
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 3
- IBMRTYCHDPMBFN-UHFFFAOYSA-N monomethyl glutaric acid Chemical compound COC(=O)CCCC(O)=O IBMRTYCHDPMBFN-UHFFFAOYSA-N 0.000 description 3
- PEZNEXFPRSOYPL-UHFFFAOYSA-N (bis(trifluoroacetoxy)iodo)benzene Chemical compound FC(F)(F)C(=O)OI(OC(=O)C(F)(F)F)C1=CC=CC=C1 PEZNEXFPRSOYPL-UHFFFAOYSA-N 0.000 description 2
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- 238000007167 Hofmann rearrangement reaction Methods 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000003810 ethyl acetate extraction Methods 0.000 description 2
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- 238000006969 Curtius rearrangement reaction Methods 0.000 description 1
- 101100391174 Dictyostelium discoideum forC gene Proteins 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 102000018997 Growth Hormone Human genes 0.000 description 1
- 108010051696 Growth Hormone Proteins 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 230000008344 brain blood flow Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 239000000122 growth hormone Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000001228 trophic effect Effects 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
Claims (15)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN200910080236XA CN101514167B (zh) | 2009-03-17 | 2009-03-17 | 手性巴氯芬的制备方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN200910080236XA CN101514167B (zh) | 2009-03-17 | 2009-03-17 | 手性巴氯芬的制备方法 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201210351053.9A Division CN102863347B (zh) | 2009-03-17 | 2009-03-17 | 手性巴氯芬的制备方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN101514167A true CN101514167A (zh) | 2009-08-26 |
CN101514167B CN101514167B (zh) | 2012-11-28 |
Family
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN200910080236XA Active CN101514167B (zh) | 2009-03-17 | 2009-03-17 | 手性巴氯芬的制备方法 |
Country Status (1)
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CN (1) | CN101514167B (zh) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2011078172A1 (ja) * | 2009-12-25 | 2011-06-30 | 株式会社カネカ | 光学活性3-置換グルタル酸モノアミドの製造法 |
WO2017009753A1 (en) | 2015-07-13 | 2017-01-19 | Piramal Enterprises Limited | An improved process for the preparation of baclofen and its intermediate |
CN109689620A (zh) * | 2016-07-22 | 2019-04-26 | 国立鲁昂大学 | 拆分巴氯芬盐的方法 |
-
2009
- 2009-03-17 CN CN200910080236XA patent/CN101514167B/zh active Active
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2011078172A1 (ja) * | 2009-12-25 | 2011-06-30 | 株式会社カネカ | 光学活性3-置換グルタル酸モノアミドの製造法 |
WO2017009753A1 (en) | 2015-07-13 | 2017-01-19 | Piramal Enterprises Limited | An improved process for the preparation of baclofen and its intermediate |
CN109689620A (zh) * | 2016-07-22 | 2019-04-26 | 国立鲁昂大学 | 拆分巴氯芬盐的方法 |
Also Published As
Publication number | Publication date |
---|---|
CN101514167B (zh) | 2012-11-28 |
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Legal Events
Date | Code | Title | Description |
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C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
C56 | Change in the name or address of the patentee | ||
CP02 | Change in the address of a patent holder |
Address after: 102206 B101 room, innovation building, Zhongguancun Life Science Park, No. 29, life science Road, Beijing, Changping District Patentee after: Meng Kun Address before: 100085 A205 room two, A District, Zhongguancun biomedicine Park, 5 Haidian District Road, Beijing, China Patentee before: Meng Kun |
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DD01 | Delivery of document by public notice |
Addressee: Meng Kun Document name: Notification of Passing Examination on Formalities |
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PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: Preparation method of chiral baclofen Effective date of registration: 20150410 Granted publication date: 20121128 Pledgee: Beijing Intellectual Property Management Co.,Ltd. Pledgor: Meng Kun Registration number: 2015990000273 |
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PLDC | Enforcement, change and cancellation of contracts on pledge of patent right or utility model | ||
PC01 | Cancellation of the registration of the contract for pledge of patent right |
Date of cancellation: 20160511 Granted publication date: 20121128 Pledgee: Beijing Intellectual Property Management Co.,Ltd. Pledgor: Meng Kun Registration number: 2015990000273 |
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PLDC | Enforcement, change and cancellation of contracts on pledge of patent right or utility model | ||
DD01 | Delivery of document by public notice |
Addressee: Tuo Ya Document name: payment instructions |
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DD01 | Delivery of document by public notice |