DK2585452T3 - Fremgangsmåde til fremstillingen af propionsyrederivater - Google Patents
Fremgangsmåde til fremstillingen af propionsyrederivater Download PDFInfo
- Publication number
- DK2585452T3 DK2585452T3 DK11703429.8T DK11703429T DK2585452T3 DK 2585452 T3 DK2585452 T3 DK 2585452T3 DK 11703429 T DK11703429 T DK 11703429T DK 2585452 T3 DK2585452 T3 DK 2585452T3
- Authority
- DK
- Denmark
- Prior art keywords
- phenyl
- mmol
- cod
- formula
- dihydro
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 27
- 238000002360 preparation method Methods 0.000 title claims description 14
- 239000004912 1,5-cyclooctadiene Substances 0.000 claims description 62
- -1 3,5-dimethylphenyl Chemical group 0.000 claims description 38
- 150000001875 compounds Chemical class 0.000 claims description 28
- 239000003054 catalyst Substances 0.000 claims description 25
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- VYXHVRARDIDEHS-UHFFFAOYSA-N 1,5-cyclooctadiene Chemical compound C1CC=CCCC=C1 VYXHVRARDIDEHS-UHFFFAOYSA-N 0.000 claims description 11
- 229910052741 iridium Inorganic materials 0.000 claims description 11
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 claims description 11
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- 125000003118 aryl group Chemical group 0.000 claims description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 4
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims description 4
- PRBHEGAFLDMLAL-UHFFFAOYSA-N 1,5-Hexadiene Natural products CC=CCC=C PRBHEGAFLDMLAL-UHFFFAOYSA-N 0.000 claims description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical group [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 3
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical group [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 claims description 3
- PYGSKMBEVAICCR-UHFFFAOYSA-N hexa-1,5-diene Chemical compound C=CCCC=C PYGSKMBEVAICCR-UHFFFAOYSA-N 0.000 claims description 3
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical group I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 3
- SJYNFBVQFBRSIB-UHFFFAOYSA-N norbornadiene Chemical compound C1=CC2C=CC1C2 SJYNFBVQFBRSIB-UHFFFAOYSA-N 0.000 claims description 3
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical group [Pd].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.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 claims description 2
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 2
- 239000005977 Ethylene Substances 0.000 claims description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical group [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 2
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 2
- 150000001805 chlorine compounds Chemical group 0.000 claims description 2
- URYYVOIYTNXXBN-UPHRSURJSA-N cyclooctene Chemical compound C1CCC\C=C/CC1 URYYVOIYTNXXBN-UPHRSURJSA-N 0.000 claims description 2
- 239000004913 cyclooctene Substances 0.000 claims description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 claims description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 claims description 2
- KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 claims description 2
- MLGJGQBMNBSEKK-UHFFFAOYSA-N [2'-(3,5-ditert-butylphenyl)spiro[1,2-dihydroindene-3,3'-1H-indene]-2'-yl]phosphane Chemical compound C(C)(C)(C)C=1C=C(C=C(C=1)C(C)(C)C)C1(C2(C3=CC=CC=C3C1)CCC1=CC=CC=C12)P MLGJGQBMNBSEKK-UHFFFAOYSA-N 0.000 claims 6
- QGHDLJAZIIFENW-UHFFFAOYSA-N 4-[1,1,1,3,3,3-hexafluoro-2-(4-hydroxy-3-prop-2-enylphenyl)propan-2-yl]-2-prop-2-enylphenol Chemical group C1=C(CC=C)C(O)=CC=C1C(C(F)(F)F)(C(F)(F)F)C1=CC=C(O)C(CC=C)=C1 QGHDLJAZIIFENW-UHFFFAOYSA-N 0.000 claims 1
- HFKJQIJFRMRSKM-UHFFFAOYSA-N [3,5-bis(trifluoromethyl)phenoxy]boronic acid Chemical compound OB(O)OC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 HFKJQIJFRMRSKM-UHFFFAOYSA-N 0.000 claims 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 63
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 48
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 42
- 239000003446 ligand Substances 0.000 description 23
- 239000007787 solid Substances 0.000 description 22
- 239000000126 substance Substances 0.000 description 20
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 20
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 19
- 239000002253 acid Substances 0.000 description 19
- 229910052739 hydrogen Inorganic materials 0.000 description 18
- 239000001257 hydrogen Substances 0.000 description 18
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
- 238000005984 hydrogenation reaction Methods 0.000 description 17
- 229910052717 sulfur Inorganic materials 0.000 description 16
- DAYKLWSKQJBGCS-NRFANRHFSA-N aleglitazar Chemical compound C1=2C=CSC=2C(C[C@H](OC)C(O)=O)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 DAYKLWSKQJBGCS-NRFANRHFSA-N 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 15
- RQEUFEKYXDPUSK-ZETCQYMHSA-N (1S)-1-phenylethanamine Chemical compound C[C@H](N)C1=CC=CC=C1 RQEUFEKYXDPUSK-ZETCQYMHSA-N 0.000 description 13
- IQEZUECHENTHPH-STZFKDTASA-N (z)-2-methoxy-3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]-1-benzothiophen-7-yl]prop-2-enoic acid Chemical compound C1=2C=CSC=2C(\C=C(/OC)C(O)=O)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 IQEZUECHENTHPH-STZFKDTASA-N 0.000 description 13
- 229910001220 stainless steel Inorganic materials 0.000 description 13
- 239000010935 stainless steel Substances 0.000 description 13
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- 239000012043 crude product Substances 0.000 description 10
- 238000004679 31P NMR spectroscopy Methods 0.000 description 8
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 8
- 238000004252 FT/ICR mass spectrometry Methods 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 239000013078 crystal Substances 0.000 description 7
- 239000012065 filter cake Substances 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- DAYKLWSKQJBGCS-OAQYLSRUSA-N (2r)-2-methoxy-3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]-1-benzothiophen-7-yl]propanoic acid Chemical compound C1=2C=CSC=2C(C[C@@H](OC)C(O)=O)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 DAYKLWSKQJBGCS-OAQYLSRUSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- DTDVMWPIIKBBIA-UHFFFAOYSA-N 3,3'-spirobi[1,2-dihydroindene]-2'-ylphosphane Chemical compound C1CC2=CC=CC=C2C21C1=CC=CC=C1CC2P DTDVMWPIIKBBIA-UHFFFAOYSA-N 0.000 description 5
- 125000003545 alkoxy group Chemical group 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 125000001072 heteroaryl group Chemical group 0.000 description 4
- 150000002503 iridium Chemical class 0.000 description 4
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 4
- 229940011051 isopropyl acetate Drugs 0.000 description 4
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 230000035484 reaction time Effects 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 125000002827 triflate group Chemical group FC(S(=O)(=O)O*)(F)F 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 229910001494 silver tetrafluoroborate Inorganic materials 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 2
- DAYKLWSKQJBGCS-UHFFFAOYSA-N 2-methoxy-3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]-1-benzothiophen-7-yl]propanoic acid Chemical compound C1=2C=CSC=2C(CC(OC)C(O)=O)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 DAYKLWSKQJBGCS-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-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
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 239000005864 Sulphur Substances 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 239000003849 aromatic solvent Substances 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 239000012455 biphasic mixture Substances 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical group 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- LLYCMZGLHLKPPU-UHFFFAOYSA-M perbromate Chemical group [O-]Br(=O)(=O)=O LLYCMZGLHLKPPU-UHFFFAOYSA-M 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 239000011574 phosphorus Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 229910001495 sodium tetrafluoroborate Inorganic materials 0.000 description 2
- RRKODOZNUZCUBN-CCAGOZQPSA-N (1z,3z)-cycloocta-1,3-diene Chemical compound C1CC\C=C/C=C\C1 RRKODOZNUZCUBN-CCAGOZQPSA-N 0.000 description 1
- IQEZUECHENTHPH-KGENOOAVSA-N (e)-2-methoxy-3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]-1-benzothiophen-7-yl]prop-2-enoic acid Chemical compound C1=2C=CSC=2C(/C=C(/OC)C(O)=O)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 IQEZUECHENTHPH-KGENOOAVSA-N 0.000 description 1
- POILWHVDKZOXJZ-ARJAWSKDSA-M (z)-4-oxopent-2-en-2-olate Chemical group C\C([O-])=C\C(C)=O POILWHVDKZOXJZ-ARJAWSKDSA-M 0.000 description 1
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- NHFAABIHBNXKDT-UHFFFAOYSA-N 4,5-dihydro-1,3-oxazole;phosphane Chemical compound P.C1CN=CO1 NHFAABIHBNXKDT-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- IXYQKKXRNHVAGP-UHFFFAOYSA-N C12(CCC3=CC=CC=C13)CCC1=CC=CC=C12.P Chemical compound C12(CCC3=CC=CC=C13)CCC1=CC=CC=C12.P IXYQKKXRNHVAGP-UHFFFAOYSA-N 0.000 description 1
- 241000276484 Gadus ogac Species 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical group [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 241000233805 Phoenix Species 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 238000009876 asymmetric hydrogenation reaction Methods 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- CZKMPDNXOGQMFW-UHFFFAOYSA-N chloro(triethyl)germane Chemical compound CC[Ge](Cl)(CC)CC CZKMPDNXOGQMFW-UHFFFAOYSA-N 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 150000001983 dialkylethers Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical group OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 238000006053 organic reaction Methods 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 150000003303 ruthenium Chemical class 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical class CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Claims (7)
1. Fremgangsmåde til fremstillingen afen forbindelse med formel (I)
eller et salt deraf, hvor en forbindelse med formel (II)
eller et salt deraf hydrogeneres i tilstedeværelse af en katalysator omfattende iridium og en forbindelse med formel (X)
hvor R1 er alkyl, aryl eller arylalkyl; og R2 er aryl.
2. Fremgangsmåde ifølge krav 1, hvor R1 er iso-pro py I, phenyl eller benzyl.
3. Fremgangsmåde ifølge krav 1 eller 2, hvor R2 er phenyl, 3,5-di-methylphenyl eller 3,5-di-tert-butyl-phenyl.
4. Fremgangsmåde ifølge et hvilket som helst af kravene 1 til 3, hvor forbindelsen med formel (X) er (Sa,R)-7-[4,5-dihyd ro-4-benzyloxazol-2-yl]-7'-diphenylphosphino-l,l' spirobiindan; (Sa,R)-7-[4,5-dihyd ro-4-benzyloxazol-2-yl]-7'-di(3,5-dimethylphenyl)phosphino-Ι,Γ-spirobiindan; (Sa,R)-7-[4,5-dihydro-4-benzyloxazol-2-yl]-7'-di(3,5-di-tert-butylphenyl) phosphino-l,l'-spirobiindan; (Sa,R)-7-[4,5-dihydro-4-phenyloxazol-2-yl]-7'-di(3,5-di-tert-butylphenyl) phosphino-l,l'-spirobiindan; eller (Sa,R)-7-[4,5-dihydro-4-isopropyloxazol-2-yl]-7'-di(3,5-di-tert-butylphenyl) phosphino-l,l'-spirobiindan.
5. Fremgangsmåde ifølge et hvilket som helst af kravene 1 til 4, hvor katalysatoren er IrfL1) (L2)nY hvor L1 er en forbindelse med formel (X) ifølge i et hvilket som helst af kravene 1 til 4; L2 er cycloocten, 1,5-cyclooctadien, ethylen, 1,5-hexadien eller norbornadien; Y er chlorid, iodid, bromid, fluorid, trifluoracetat, tetrafluorborat, tetrakis[3,5-bis(trifluormethyl)phenyl]borat, tetraphenylborat, hexafluorantimonat, hexafluorphosphat, triflat, mesylat, perchlorat, perbromat, periodat, nitrat, hydrogensulfat eller acetylacetonat; og n er 1 eller 2.
6. Fremgangsmåde ifølge et hvilket som helst af kravene 1 til 5, hvor katalysatoren er [Ir((Sa,R)-7-[4,5-dihydro-4-benzyloxazol-2-yl]-7'-di(3,5-di-tert-butylphenyl) phosphino-l,r-spirobiindan)(l,5-cyclooctadien)][tetrakis[3,5-bis(trifluormethyl)phenyl] borat]; [Ir((Sa,R)-7-[4,5-dihydro-4-benzyloxazol-2-yl]-7'-di(3,5-di-tert-butylphenyl) phosphino-l,l'-spirobiindan)( 1,5-cyclooctadien)] [tetrafluorborat]; [Ir((Sa,R)-7-[4,5-dihydro-4-benzyloxazol-2-yl]-7'-di(3,5-di-tert-butylphenyl) phosphino-l,l'-spirobiindan)( 1,5-cyclooctadien)] [trifluormethansulfonat]; eller [Ir((Sa,R)-7-[4,5-dihydro-4-benzyloxazol-2-yl]-7'-di(3,5-di-tert-butylphenyl) phosphino-l,l'-spirobiindan)(l,5-cyclooctadien)][chlorid].
7. Anvendelsen afen katalysator ifølge i et hvilket som helst af kravene 1 til 6 til fremstillingen afen forbindelse med formel (I) ifølge krav 1.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP09178220 | 2009-12-07 | ||
| PCT/EP2011/051610 WO2011070179A1 (en) | 2009-12-07 | 2011-02-03 | Process for the preparation of propionic acid derivatives |
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| Publication Number | Publication Date |
|---|---|
| DK2585452T3 true DK2585452T3 (da) | 2015-10-12 |
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| Application Number | Title | Priority Date | Filing Date |
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| DK11703429.8T DK2585452T3 (da) | 2009-12-07 | 2011-02-03 | Fremgangsmåde til fremstillingen af propionsyrederivater |
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| Country | Link |
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| EP (1) | EP2585452B1 (da) |
| AU (1) | AU2011203002B2 (da) |
| CA (1) | CA2783448C (da) |
| DK (1) | DK2585452T3 (da) |
| ES (1) | ES2552310T3 (da) |
| HU (1) | HUE025399T2 (da) |
| IL (1) | IL220015A0 (da) |
| MY (1) | MY181791A (da) |
| NZ (1) | NZ600273A (da) |
| PL (1) | PL2585452T3 (da) |
| SG (1) | SG182259A1 (da) |
| SI (1) | SI2585452T1 (da) |
| WO (1) | WO2011070179A1 (da) |
| ZA (1) | ZA201205062B (da) |
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| WO2013181384A1 (en) | 2012-05-31 | 2013-12-05 | Ratiopharm Gmbh | Solid state forms of aleglitazar sodium |
| BR112015005350A2 (pt) * | 2012-09-12 | 2017-07-04 | Hoffmann La Roche | formas sólidas de (s)-2-metoxi-3-{4-[2-(5-metil-2-feniloxazol-4-ila)-etoxi]-benzo[b]tiofen-7-ila}-ácido propiônico e/ou sais do mesmo |
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| DE60211891T2 (de) | 2001-05-15 | 2007-05-24 | F. Hoffmann-La Roche Ag | Carbonsäure-substituierte oxazol-derivate zur verwendung als ppar-alpha und -gamma aktivatoren zur behandlung von diabetes |
| US7262303B2 (en) | 2003-09-29 | 2007-08-28 | Hoffman-La Roche Inc. | Process for the production of chiral propionic acid derivatives |
| CN101565434B (zh) * | 2008-04-25 | 2012-05-30 | 浙江九洲药业股份有限公司 | 螺环膦-噁唑啉和制备方法及其应用 |
| US8450496B2 (en) * | 2009-03-24 | 2013-05-28 | Hoffman-La Roche Inc. | Process for the preparation of propionic acid derivatives |
-
2011
- 2011-02-03 SI SI201130647T patent/SI2585452T1/sl unknown
- 2011-02-03 EP EP11703429.8A patent/EP2585452B1/en not_active Not-in-force
- 2011-02-03 CA CA2783448A patent/CA2783448C/en not_active Expired - Fee Related
- 2011-02-03 AU AU2011203002A patent/AU2011203002B2/en not_active Ceased
- 2011-02-03 SG SG2012041943A patent/SG182259A1/en unknown
- 2011-02-03 DK DK11703429.8T patent/DK2585452T3/da active
- 2011-02-03 HU HUE11703429A patent/HUE025399T2/en unknown
- 2011-02-03 NZ NZ600273A patent/NZ600273A/en not_active IP Right Cessation
- 2011-02-03 WO PCT/EP2011/051610 patent/WO2011070179A1/en not_active Ceased
- 2011-02-03 ES ES11703429.8T patent/ES2552310T3/es active Active
- 2011-02-03 PL PL11703429T patent/PL2585452T3/pl unknown
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2012
- 2012-05-24 IL IL220015A patent/IL220015A0/en not_active IP Right Cessation
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Also Published As
| Publication number | Publication date |
|---|---|
| WO2011070179A1 (en) | 2011-06-16 |
| RU2012128354A (ru) | 2014-01-20 |
| ES2552310T3 (es) | 2015-11-27 |
| ZA201205062B (en) | 2013-03-27 |
| HUE025399T2 (en) | 2016-02-29 |
| MY181791A (en) | 2021-01-07 |
| EP2585452B1 (en) | 2015-09-23 |
| CA2783448A1 (en) | 2011-06-16 |
| CA2783448C (en) | 2018-11-20 |
| EP2585452A1 (en) | 2013-05-01 |
| PL2585452T3 (pl) | 2016-03-31 |
| SG182259A1 (en) | 2012-08-30 |
| IL220015A0 (en) | 2012-07-31 |
| NZ600273A (en) | 2014-03-28 |
| WO2011070179A8 (en) | 2013-04-04 |
| AU2011203002B2 (en) | 2014-09-04 |
| AU2011203002A1 (en) | 2012-06-07 |
| SI2585452T1 (sl) | 2015-12-31 |
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