JP2003342259A - 光学活性シスピペリジン誘導体の製造法 - Google Patents
光学活性シスピペリジン誘導体の製造法Info
- Publication number
- JP2003342259A JP2003342259A JP2002369405A JP2002369405A JP2003342259A JP 2003342259 A JP2003342259 A JP 2003342259A JP 2002369405 A JP2002369405 A JP 2002369405A JP 2002369405 A JP2002369405 A JP 2002369405A JP 2003342259 A JP2003342259 A JP 2003342259A
- Authority
- JP
- Japan
- Prior art keywords
- optically active
- group
- derivative
- amino
- tartaric acid
- 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.)
- Pending
Links
- 238000004519 manufacturing process Methods 0.000 title claims description 11
- 230000003287 optical effect Effects 0.000 claims abstract description 47
- 239000000203 mixture Substances 0.000 claims abstract description 29
- 238000000034 method Methods 0.000 claims abstract description 20
- 150000003862 amino acid derivatives Chemical class 0.000 claims abstract description 19
- 150000003892 tartrate salts Chemical class 0.000 claims abstract description 12
- PICQEJDBZKDWOD-AWEZNQCLSA-N (2s)-2-(benzenesulfonamido)-3-phenylpropanoic acid Chemical compound C([C@@H](C(=O)O)NS(=O)(=O)C=1C=CC=CC=1)C1=CC=CC=C1 PICQEJDBZKDWOD-AWEZNQCLSA-N 0.000 claims abstract description 6
- CCIUQRKCMXXTOI-UHFFFAOYSA-N 2,3-dihydroxy-2,3-bis(4-methoxybenzoyl)butanedioic acid Chemical compound C1=CC(OC)=CC=C1C(=O)C(O)(C(O)=O)C(O)(C(O)=O)C(=O)C1=CC=C(OC)C=C1 CCIUQRKCMXXTOI-UHFFFAOYSA-N 0.000 claims abstract description 4
- NTOIKDYVJIWVSU-UHFFFAOYSA-N 2,3-dihydroxy-2,3-bis(4-methylbenzoyl)butanedioic acid Chemical compound C1=CC(C)=CC=C1C(=O)C(O)(C(O)=O)C(O)(C(O)=O)C(=O)C1=CC=C(C)C=C1 NTOIKDYVJIWVSU-UHFFFAOYSA-N 0.000 claims abstract description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 48
- GFMAFYNUQDLPBP-QWRGUYRKSA-N (2s,3s)-2-phenylpiperidin-3-amine Chemical compound N[C@H]1CCCN[C@H]1C1=CC=CC=C1 GFMAFYNUQDLPBP-QWRGUYRKSA-N 0.000 claims description 28
- -1 2-methoxybenzoyl Chemical group 0.000 claims description 22
- 125000004432 carbon atom Chemical group C* 0.000 claims description 17
- 239000002904 solvent Substances 0.000 claims description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 12
- 125000003118 aryl group Chemical group 0.000 claims description 11
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 10
- 229910052799 carbon Inorganic materials 0.000 claims description 10
- 150000001721 carbon Chemical group 0.000 claims description 10
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- 125000002252 acyl group Chemical group 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- ICFOBMSVJMGIMX-HNNXBMFYSA-N (2s)-2-(benzylsulfonylamino)-3-phenylpropanoic acid Chemical compound C([C@@H](C(=O)O)NS(=O)(=O)CC=1C=CC=CC=1)C1=CC=CC=C1 ICFOBMSVJMGIMX-HNNXBMFYSA-N 0.000 claims description 5
- ZCOVHLPDAJWNFS-JTQLQIEISA-N (2s)-2-(benzylsulfonylamino)pentanedioic acid Chemical compound OC(=O)CC[C@@H](C(O)=O)NS(=O)(=O)CC1=CC=CC=C1 ZCOVHLPDAJWNFS-JTQLQIEISA-N 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- RBLNYXNJCNZJDD-VIFPVBQESA-N (2s)-2-(benzylsulfonylamino)butanedioic acid Chemical compound OC(=O)C[C@@H](C(O)=O)NS(=O)(=O)CC1=CC=CC=C1 RBLNYXNJCNZJDD-VIFPVBQESA-N 0.000 claims description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 4
- 239000003054 catalyst Substances 0.000 claims description 4
- 238000005984 hydrogenation reaction Methods 0.000 claims description 4
- PJLOGZZDKDUMFU-VIFPVBQESA-N (2s)-2-(benzenesulfonamido)pentanedioic acid Chemical compound OC(=O)CC[C@@H](C(O)=O)NS(=O)(=O)C1=CC=CC=C1 PJLOGZZDKDUMFU-VIFPVBQESA-N 0.000 claims description 3
- WMJNKBXKYHXOHC-UHFFFAOYSA-N 2,3-dihydroxy-2,3-bis(2-methylbenzoyl)butanedioic acid Chemical compound CC1=CC=CC=C1C(=O)C(O)(C(O)=O)C(O)(C(O)=O)C(=O)C1=CC=CC=C1C WMJNKBXKYHXOHC-UHFFFAOYSA-N 0.000 claims description 3
- HYQFZIWQHXXBER-UHFFFAOYSA-N 2,3-dihydroxy-2,3-bis(3-methoxybenzoyl)butanedioic acid Chemical compound COC1=CC=CC(C(=O)C(O)(C(O)=O)C(O)(C(O)=O)C(=O)C=2C=C(OC)C=CC=2)=C1 HYQFZIWQHXXBER-UHFFFAOYSA-N 0.000 claims description 3
- QJBGCXNTFZBQJR-UHFFFAOYSA-N 2-(benzenesulfonamido)-2-phenylacetic acid Chemical compound C=1C=CC=CC=1C(C(=O)O)NS(=O)(=O)C1=CC=CC=C1 QJBGCXNTFZBQJR-UHFFFAOYSA-N 0.000 claims description 3
- GNKIIMLQXMFHLQ-UHFFFAOYSA-N 2-(benzylsulfonylamino)-2-phenylacetic acid Chemical compound C=1C=CC=CC=1C(C(=O)O)NS(=O)(=O)CC1=CC=CC=C1 GNKIIMLQXMFHLQ-UHFFFAOYSA-N 0.000 claims description 3
- KMGUEILFFWDGFV-UHFFFAOYSA-N 2-benzoyl-2-benzoyloxy-3-hydroxybutanedioic acid Chemical compound C=1C=CC=CC=1C(=O)C(C(C(O)=O)O)(C(O)=O)OC(=O)C1=CC=CC=C1 KMGUEILFFWDGFV-UHFFFAOYSA-N 0.000 claims description 3
- XTHJCITVHCRQRD-UHFFFAOYSA-N 2-phenylpyridin-3-amine Chemical compound NC1=CC=CN=C1C1=CC=CC=C1 XTHJCITVHCRQRD-UHFFFAOYSA-N 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- DJLTZJGULPLVOA-UHFFFAOYSA-N N-Benzoylaspartic acid Chemical compound OC(=O)CC(C(O)=O)NC(=O)C1=CC=CC=C1 DJLTZJGULPLVOA-UHFFFAOYSA-N 0.000 claims description 3
- NPKISZUVEBESJI-AWEZNQCLSA-N N-benzoyl-L-phenylalanine Chemical compound C([C@@H](C(=O)O)NC(=O)C=1C=CC=CC=1)C1=CC=CC=C1 NPKISZUVEBESJI-AWEZNQCLSA-N 0.000 claims description 3
- NPKISZUVEBESJI-UHFFFAOYSA-N Nalpha-benzoyl-L-phenylalanine Natural products C=1C=CC=CC=1C(=O)NC(C(=O)O)CC1=CC=CC=C1 NPKISZUVEBESJI-UHFFFAOYSA-N 0.000 claims description 3
- 230000007935 neutral effect Effects 0.000 claims description 3
- 150000003053 piperidines Chemical class 0.000 claims description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
- GAUDUMMZSVZLNU-QMMMGPOBSA-N (2s)-2-(benzenesulfonamido)butanedioic acid Chemical compound OC(=O)C[C@@H](C(O)=O)NS(=O)(=O)C1=CC=CC=C1 GAUDUMMZSVZLNU-QMMMGPOBSA-N 0.000 claims description 2
- LPJXPACOXRZCCP-VIFPVBQESA-N (2s)-2-benzamidopentanedioic acid Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)C1=CC=CC=C1 LPJXPACOXRZCCP-VIFPVBQESA-N 0.000 claims description 2
- ACDLFRQZDTZESK-UHFFFAOYSA-N 2-benzamido-2-phenylacetic acid Chemical compound C=1C=CC=CC=1C(C(=O)O)NC(=O)C1=CC=CC=C1 ACDLFRQZDTZESK-UHFFFAOYSA-N 0.000 claims description 2
- ZYPJGOCQEPYWIE-UHFFFAOYSA-N 4-amino-2,3-dihydroxy-4-oxobutanoic acid Chemical class NC(=O)C(O)C(O)C(O)=O ZYPJGOCQEPYWIE-UHFFFAOYSA-N 0.000 claims description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 2
- 230000002378 acidificating effect Effects 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000003395 phenylethylamino group Chemical group [H]N(*)C([H])([H])C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 2
- 235000002906 tartaric acid Nutrition 0.000 claims description 2
- 239000011975 tartaric acid Substances 0.000 claims description 2
- DVMNOSBSAVUYEU-UHFFFAOYSA-N 2,3-dihydroxy-2,3-bis(3-methylbenzoyl)butanedioic acid Chemical compound CC1=CC=CC(C(=O)C(O)(C(O)=O)C(O)(C(O)=O)C(=O)C=2C=C(C)C=CC=2)=C1 DVMNOSBSAVUYEU-UHFFFAOYSA-N 0.000 claims 1
- XQDSIGDVDWFZPP-UHFFFAOYSA-N 2-phenylpiperidin-1-amine Chemical compound NN1CCCCC1C1=CC=CC=C1 XQDSIGDVDWFZPP-UHFFFAOYSA-N 0.000 claims 1
- 239000000126 substance Substances 0.000 abstract description 21
- 238000009776 industrial production Methods 0.000 abstract description 4
- 150000003839 salts Chemical class 0.000 description 49
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 34
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- 239000013078 crystal Substances 0.000 description 23
- GFMAFYNUQDLPBP-UHFFFAOYSA-N 2-phenylpiperidin-3-amine Chemical compound NC1CCCNC1C1=CC=CC=C1 GFMAFYNUQDLPBP-UHFFFAOYSA-N 0.000 description 22
- 239000003795 chemical substances by application Substances 0.000 description 16
- 238000003756 stirring Methods 0.000 description 14
- 238000004817 gas chromatography Methods 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 7
- 238000000926 separation method Methods 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- WGIAUTGOUJDVEI-UHFFFAOYSA-N 2-phenylpiperidine Chemical compound N1CCCCC1C1=CC=CC=C1 WGIAUTGOUJDVEI-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 239000007788 liquid Substances 0.000 description 5
- 239000002994 raw material Substances 0.000 description 5
- VQGHOUODWALEFC-UHFFFAOYSA-N 2-phenylpyridine Chemical compound C1=CC=CC=C1C1=CC=CC=N1 VQGHOUODWALEFC-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 229960005261 aspartic acid Drugs 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- PICQEJDBZKDWOD-CQSZACIVSA-N (2r)-2-(benzenesulfonamido)-3-phenylpropanoic acid Chemical compound C([C@H](C(=O)O)NS(=O)(=O)C=1C=CC=CC=1)C1=CC=CC=C1 PICQEJDBZKDWOD-CQSZACIVSA-N 0.000 description 3
- MEQBJJUWDCYIAB-UHFFFAOYSA-N 2-chloropyridin-3-amine Chemical compound NC1=CC=CN=C1Cl MEQBJJUWDCYIAB-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 235000003704 aspartic acid Nutrition 0.000 description 3
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- UKQPNXSQGUFKPM-UHFFFAOYSA-N n-methyl-2-phenylpiperidin-3-amine Chemical compound CNC1CCCNC1C1=CC=CC=C1 UKQPNXSQGUFKPM-UHFFFAOYSA-N 0.000 description 3
- SYTBZMRGLBWNTM-SNVBAGLBSA-N (R)-flurbiprofen Chemical compound FC1=CC([C@H](C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-SNVBAGLBSA-N 0.000 description 2
- DVFMYDXKJZNVGI-UHFFFAOYSA-N 2,3-dihydroxy-2,3-bis(2-methoxybenzoyl)butanedioic acid Chemical compound COC1=CC=CC=C1C(=O)C(O)(C(O)=O)C(O)(C(O)=O)C(=O)C1=CC=CC=C1OC DVFMYDXKJZNVGI-UHFFFAOYSA-N 0.000 description 2
- GFMSRLFQVPVUHZ-UHFFFAOYSA-N 2-cyclohexylpiperidin-3-amine Chemical compound NC1CCCNC1C1CCCCC1 GFMSRLFQVPVUHZ-UHFFFAOYSA-N 0.000 description 2
- HHSOUQXZVNRLQM-UHFFFAOYSA-N CC1=CC(C(C(C(O)=O)(C2=CC=CC(C)=C2)O)(C(O)=O)O)=CC=C1 Chemical compound CC1=CC(C(C(C(O)=O)(C2=CC=CC(C)=C2)O)(C(O)=O)O)=CC=C1 HHSOUQXZVNRLQM-UHFFFAOYSA-N 0.000 description 2
- NSTPXGARCQOSAU-UHFFFAOYSA-N N-Formyl-Phenylalanine Natural products O=CNC(C(=O)O)CC1=CC=CC=C1 NSTPXGARCQOSAU-UHFFFAOYSA-N 0.000 description 2
- NSTPXGARCQOSAU-VIFPVBQESA-N N-formyl-L-phenylalanine Chemical compound O=CN[C@H](C(=O)O)CC1=CC=CC=C1 NSTPXGARCQOSAU-VIFPVBQESA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 229960005190 phenylalanine Drugs 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- DNISEZBAYYIQFB-PHDIDXHHSA-N (2r,3r)-2,3-diacetyloxybutanedioic acid Chemical compound CC(=O)O[C@@H](C(O)=O)[C@H](C(O)=O)OC(C)=O DNISEZBAYYIQFB-PHDIDXHHSA-N 0.000 description 1
- IWYDHOAUDWTVEP-ZETCQYMHSA-N (S)-mandelic acid Chemical compound OC(=O)[C@@H](O)C1=CC=CC=C1 IWYDHOAUDWTVEP-ZETCQYMHSA-N 0.000 description 1
- LLSKXGRDUPMXLC-UHFFFAOYSA-N 1-phenylpiperidine Chemical compound C1CCCCN1C1=CC=CC=C1 LLSKXGRDUPMXLC-UHFFFAOYSA-N 0.000 description 1
- VOXXGUAZBWSUSS-UHFFFAOYSA-N 2,4,6-triphenyl-1,3,5,2,4,6-trioxatriborinane Chemical compound O1B(C=2C=CC=CC=2)OB(C=2C=CC=CC=2)OB1C1=CC=CC=C1 VOXXGUAZBWSUSS-UHFFFAOYSA-N 0.000 description 1
- CZHBLKINFJLTRU-UHFFFAOYSA-N 2-(3-ethyl-2-methylphenyl)piperidin-3-amine Chemical compound CCC1=CC=CC(C2C(CCCN2)N)=C1C CZHBLKINFJLTRU-UHFFFAOYSA-N 0.000 description 1
- PNDGHBKOLZNDRC-UHFFFAOYSA-N 2-(4-chlorophenyl)piperidin-3-amine Chemical compound NC1CCCNC1C1=CC=C(Cl)C=C1 PNDGHBKOLZNDRC-UHFFFAOYSA-N 0.000 description 1
- PXKWUKUIDAUOCI-UHFFFAOYSA-N 2-(4-methylphenyl)piperidin-3-amine Chemical compound C1=CC(C)=CC=C1C1C(N)CCCN1 PXKWUKUIDAUOCI-UHFFFAOYSA-N 0.000 description 1
- HUTHUTALXJNNRS-UHFFFAOYSA-N 2-cyclohexylpyridine Chemical compound C1CCCCC1C1=CC=CC=N1 HUTHUTALXJNNRS-UHFFFAOYSA-N 0.000 description 1
- AZTYHYHSDPMHRA-UHFFFAOYSA-N 2-formamido-2-phenylacetic acid Chemical compound O=CNC(C(=O)O)C1=CC=CC=C1 AZTYHYHSDPMHRA-UHFFFAOYSA-N 0.000 description 1
- MQUUQXIFCBBFDP-UHFFFAOYSA-N 2-formamidobutanedioic acid Chemical compound OC(=O)CC(C(O)=O)NC=O MQUUQXIFCBBFDP-UHFFFAOYSA-N 0.000 description 1
- ADZLWSMFHHHOBV-UHFFFAOYSA-N 2-formamidopentanedioic acid Chemical compound OC(=O)CCC(C(O)=O)NC=O ADZLWSMFHHHOBV-UHFFFAOYSA-N 0.000 description 1
- 125000001999 4-Methoxybenzoyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C(*)=O 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- ZGUNAGUHMKGQNY-ZETCQYMHSA-N L-alpha-phenylglycine zwitterion Chemical compound OC(=O)[C@@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-ZETCQYMHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical class OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- OTCCIMWXFLJLIA-UHFFFAOYSA-N N-acetyl-DL-aspartic acid Natural products CC(=O)NC(C(O)=O)CC(O)=O OTCCIMWXFLJLIA-UHFFFAOYSA-N 0.000 description 1
- VKDFZMMOLPIWQQ-VIFPVBQESA-N N-acetyl-L-alpha-phenylglycine Chemical compound CC(=O)N[C@H](C(O)=O)C1=CC=CC=C1 VKDFZMMOLPIWQQ-VIFPVBQESA-N 0.000 description 1
- OTCCIMWXFLJLIA-BYPYZUCNSA-N N-acetyl-L-aspartic acid Chemical compound CC(=O)N[C@H](C(O)=O)CC(O)=O OTCCIMWXFLJLIA-BYPYZUCNSA-N 0.000 description 1
- RFMMMVDNIPUKGG-YFKPBYRVSA-N N-acetyl-L-glutamic acid Chemical compound CC(=O)N[C@H](C(O)=O)CCC(O)=O RFMMMVDNIPUKGG-YFKPBYRVSA-N 0.000 description 1
- CBQJSKKFNMDLON-JTQLQIEISA-N N-acetyl-L-phenylalanine Chemical compound CC(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 CBQJSKKFNMDLON-JTQLQIEISA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 238000004807 desolvation Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- JVZRCNQLWOELDU-UHFFFAOYSA-N gamma-Phenylpyridine Natural products C1=CC=CC=C1C1=CC=NC=C1 JVZRCNQLWOELDU-UHFFFAOYSA-N 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 1
- 229940011051 isopropyl acetate Drugs 0.000 description 1
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000011268 mixed slurry Substances 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- UXUMJCYFONDHKI-UHFFFAOYSA-N n,n-dimethyl-2-phenylpiperidin-3-amine Chemical compound CN(C)C1CCCNC1C1=CC=CC=C1 UXUMJCYFONDHKI-UHFFFAOYSA-N 0.000 description 1
- BBYOBISKKSFQGU-UHFFFAOYSA-N n-ethyl-2-phenylpiperidin-3-amine Chemical compound CCNC1CCCNC1C1=CC=CC=C1 BBYOBISKKSFQGU-UHFFFAOYSA-N 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 1
- 150000004885 piperazines Chemical class 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
Landscapes
- Hydrogenated Pyridines (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2002369405A JP2003342259A (ja) | 2001-12-21 | 2002-12-20 | 光学活性シスピペリジン誘導体の製造法 |
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| JP2001388633 | 2001-12-21 | ||
| JP2001-388633 | 2001-12-21 | ||
| JP2002074160 | 2002-03-18 | ||
| JP2002-74160 | 2002-03-18 | ||
| JP2002369405A JP2003342259A (ja) | 2001-12-21 | 2002-12-20 | 光学活性シスピペリジン誘導体の製造法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2003342259A true JP2003342259A (ja) | 2003-12-03 |
| JP2003342259A5 JP2003342259A5 (enExample) | 2005-04-07 |
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| JP2002369405A Pending JP2003342259A (ja) | 2001-12-21 | 2002-12-20 | 光学活性シスピペリジン誘導体の製造法 |
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| Country | Link |
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| JP (1) | JP2003342259A (enExample) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2012211174A (ja) * | 2004-11-05 | 2012-11-01 | Boehringer Ingelheim Internatl Gmbh | キラル８−（３−アミノ−ピペリジン−１−イル）−キサンチンの製造方法 |
| JP2021515029A (ja) * | 2017-12-22 | 2021-06-17 | ジークフリート アクチェンゲゼルシャフトＳｉｅｇｆｒｉｅｄ Ａｇ | Ｏ，ｏ’−二置換酒石酸エナンチオマーの添加によるラセミ体ニコチンのエナンチオマー分離 |
| US11407730B2 (en) | 2017-12-22 | 2022-08-09 | Siegfried Ag | Preparation of racemic nicotine by reaction of ethyl nicotinate with N-vinylpyrrolidone in the presence of an alcoholate base and subsequent process steps |
-
2002
- 2002-12-20 JP JP2002369405A patent/JP2003342259A/ja active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2012211174A (ja) * | 2004-11-05 | 2012-11-01 | Boehringer Ingelheim Internatl Gmbh | キラル８−（３−アミノ−ピペリジン−１−イル）−キサンチンの製造方法 |
| JP2021515029A (ja) * | 2017-12-22 | 2021-06-17 | ジークフリート アクチェンゲゼルシャフトＳｉｅｇｆｒｉｅｄ Ａｇ | Ｏ，ｏ’−二置換酒石酸エナンチオマーの添加によるラセミ体ニコチンのエナンチオマー分離 |
| JP7030208B2 (ja) | 2017-12-22 | 2022-03-04 | ジークフリート アクチェンゲゼルシャフト | Ｏ，ｏ’－二置換酒石酸エナンチオマーの添加によるラセミ体ニコチンのエナンチオマー分離 |
| US11279685B2 (en) | 2017-12-22 | 2022-03-22 | Siegfried Ag | Enantiomeric separation of racemic nicotine by addition of an O,O″-disubstituted tartaric acid enantiomer |
| US11407730B2 (en) | 2017-12-22 | 2022-08-09 | Siegfried Ag | Preparation of racemic nicotine by reaction of ethyl nicotinate with N-vinylpyrrolidone in the presence of an alcoholate base and subsequent process steps |
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