WO2006014006A1 - Procédé servant à produire des aminodiols insaturés - Google Patents
Procédé servant à produire des aminodiols insaturés Download PDFInfo
- Publication number
- WO2006014006A1 WO2006014006A1 PCT/JP2005/014602 JP2005014602W WO2006014006A1 WO 2006014006 A1 WO2006014006 A1 WO 2006014006A1 JP 2005014602 W JP2005014602 W JP 2005014602W WO 2006014006 A1 WO2006014006 A1 WO 2006014006A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- nmr
- unsaturated
- aminodiols
- mmol
- group
- Prior art date
Links
- 238000004519 manufacturing process Methods 0.000 title claims description 11
- 238000005649 metathesis reaction Methods 0.000 claims abstract description 15
- 239000003054 catalyst Substances 0.000 claims abstract description 11
- 238000000034 method Methods 0.000 claims abstract description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 14
- 125000006239 protecting group Chemical group 0.000 claims description 11
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims description 7
- HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical compound [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 claims description 7
- 229910052707 ruthenium Inorganic materials 0.000 claims description 7
- 125000003118 aryl group Chemical group 0.000 claims description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- 239000003446 ligand Substances 0.000 claims description 5
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims description 5
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- 230000003197 catalytic effect Effects 0.000 claims 1
- 150000001336 alkenes Chemical class 0.000 abstract description 5
- 239000002994 raw material Substances 0.000 abstract description 5
- 238000012377 drug delivery Methods 0.000 abstract description 4
- 230000002194 synthesizing effect Effects 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 60
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 57
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 31
- 239000000243 solution Substances 0.000 description 28
- -1 unsaturated amino diols Chemical class 0.000 description 22
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- 239000011541 reaction mixture Substances 0.000 description 21
- 238000010898 silica gel chromatography Methods 0.000 description 18
- 239000000203 mixture Substances 0.000 description 15
- 239000011780 sodium chloride Substances 0.000 description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- 239000012044 organic layer Substances 0.000 description 12
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 11
- 229920006395 saturated elastomer Polymers 0.000 description 11
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
- CAAULPUQFIIOTL-UHFFFAOYSA-N methyl dihydrogen phosphate Chemical compound COP(O)(O)=O CAAULPUQFIIOTL-UHFFFAOYSA-N 0.000 description 8
- PJLHTVIBELQURV-UHFFFAOYSA-N 1-pentadecene Chemical compound CCCCCCCCCCCCCC=C PJLHTVIBELQURV-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 125000005999 2-bromoethyl group Chemical group 0.000 description 5
- 235000019270 ammonium chloride Nutrition 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- QHORRKSZGBYGPH-UHFFFAOYSA-L benzylidene(dichloro)ruthenium Chemical compound Cl[Ru](Cl)=CC1=CC=CC=C1 QHORRKSZGBYGPH-UHFFFAOYSA-L 0.000 description 4
- VHVMXWZXFBOANQ-UHFFFAOYSA-N 1-Penten-3-ol Chemical compound CCC(O)C=C VHVMXWZXFBOANQ-UHFFFAOYSA-N 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- JRZJOMJEPLMPRA-UHFFFAOYSA-N 1-nonene Chemical compound CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 2
- BPRYUXCVCCNUFE-UHFFFAOYSA-N 2,4,6-trimethylphenol Chemical compound CC1=CC(C)=C(O)C(C)=C1 BPRYUXCVCCNUFE-UHFFFAOYSA-N 0.000 description 2
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000004020 conductor Substances 0.000 description 2
- 150000002148 esters Chemical group 0.000 description 2
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 2
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 2
- HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 2
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 210000000689 upper leg Anatomy 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- VDPPIYIIIPICAT-VIFPVBQESA-N (4s)-3-benzyl-2-oxo-1,3-oxazolidine-4-carboxylic acid Chemical compound OC(=O)[C@@H]1COC(=O)N1CC1=CC=CC=C1 VDPPIYIIIPICAT-VIFPVBQESA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- AUPAYCJYILOTQL-UHFFFAOYSA-N 1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazole Chemical compound CC1=CC(C)=CC(C)=C1N1CCN(C=2C(=CC(C)=CC=2C)C)[CH]1 AUPAYCJYILOTQL-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- LIKMAJRDDDTEIG-UHFFFAOYSA-N 1-hexene Chemical compound CCCCC=C LIKMAJRDDDTEIG-UHFFFAOYSA-N 0.000 description 1
- GIEMHYCMBGELGY-UHFFFAOYSA-N 10-undecen-1-ol Chemical compound OCCCCCCCCCC=C GIEMHYCMBGELGY-UHFFFAOYSA-N 0.000 description 1
- LZFZQYNTEZSWCP-UHFFFAOYSA-N 2,6-dibutyl-4-methylphenol Chemical compound CCCCC1=CC(C)=CC(CCCC)=C1O LZFZQYNTEZSWCP-UHFFFAOYSA-N 0.000 description 1
- HQAXHIGPGBPPFU-UHFFFAOYSA-N 2-prop-2-ynoxyoxane Chemical compound C#CCOC1CCCCO1 HQAXHIGPGBPPFU-UHFFFAOYSA-N 0.000 description 1
- DDFHBQSCUXNBSA-UHFFFAOYSA-N 5-(5-carboxythiophen-2-yl)thiophene-2-carboxylic acid Chemical compound S1C(C(=O)O)=CC=C1C1=CC=C(C(O)=O)S1 DDFHBQSCUXNBSA-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- VHCQVGQULWFQTM-UHFFFAOYSA-N Rubone Natural products COC1=CC(OC)=CC(O)=C1C(=O)C=CC1=CC(OC)=C(OC)C=C1OC VHCQVGQULWFQTM-UHFFFAOYSA-N 0.000 description 1
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 1
- 125000002015 acyclic group Chemical group 0.000 description 1
- 238000005575 aldol reaction Methods 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- GETQZCLCWQTVFV-UHFFFAOYSA-N anhydrous trimethylamine Natural products CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 1
- 125000000649 benzylidene group Chemical group [H]C(=[*])C1=C([H])C([H])=C([H])C([H])=C1[H] 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
- 125000004744 butyloxycarbonyl group Chemical group 0.000 description 1
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000004210 ether based solvent Substances 0.000 description 1
- 125000001033 ether group Chemical group 0.000 description 1
- 125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- ARBOVOVUTSQWSS-UHFFFAOYSA-N hexadecanoyl chloride Chemical compound CCCCCCCCCCCCCCCC(Cl)=O ARBOVOVUTSQWSS-UHFFFAOYSA-N 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 230000036632 reaction speed Effects 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000005870 sharpless asymmetric epoxidation reaction Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 125000004469 siloxy group Chemical group [SiH3]O* 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- PNJXYVJNOCLJLJ-QMMMGPOBSA-N tert-butyl (4r)-4-formyl-2,2-dimethyl-1,3-oxazolidine-3-carboxylate Chemical compound CC(C)(C)OC(=O)N1[C@@H](C=O)COC1(C)C PNJXYVJNOCLJLJ-QMMMGPOBSA-N 0.000 description 1
- OKFPLDLNECXROG-VFPASMGPSA-N tert-butyl N-[(E,2S,3R)-1,3-dihydroxyhex-4-en-2-yl]carbamate Chemical compound C\C=C\[C@@H](O)[C@H](CO)NC(=O)OC(C)(C)C OKFPLDLNECXROG-VFPASMGPSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- UMUDVBSIURBUGW-BWMVHVDHSA-N tert-butyl n-[(e,2s,3r)-1,3-dihydroxyoctadec-4-en-2-yl]carbamate Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@H](CO)NC(=O)OC(C)(C)C UMUDVBSIURBUGW-BWMVHVDHSA-N 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- 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
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/22—Organic complexes
- B01J31/2265—Carbenes or carbynes, i.e.(image)
- B01J31/2278—Complexes comprising two carbene ligands differing from each other, e.g. Grubbs second generation catalysts
-
- 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
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/22—Organic complexes
- B01J31/2265—Carbenes or carbynes, i.e.(image)
- B01J31/2269—Heterocyclic carbenes
- B01J31/2273—Heterocyclic carbenes with only nitrogen as heteroatomic ring members, e.g. 1,3-diarylimidazoline-2-ylidenes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C269/00—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C269/06—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups by reactions not involving the formation of carbamate groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
- C07F7/1872—Preparation; Treatments not provided for in C07F7/20
- C07F7/1892—Preparation; Treatments not provided for in C07F7/20 by reactions not provided for in C07F7/1876 - C07F7/1888
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/08—Esters of oxyacids of phosphorus
- C07F9/09—Esters of phosphoric acids
- C07F9/113—Esters of phosphoric acids with unsaturated acyclic alcohols
-
- 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
- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
- B01J2231/50—Redistribution or isomerisation reactions of C-C, C=C or C-C triple bonds
- B01J2231/54—Metathesis reactions, e.g. olefin metathesis
- B01J2231/543—Metathesis reactions, e.g. olefin metathesis alkene metathesis
-
- 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
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/80—Complexes comprising metals of Group VIII as the central metal
- B01J2531/82—Metals of the platinum group
- B01J2531/821—Ruthenium
Definitions
- the present invention relates to a method for producing unsaturated aminodiols utilizing a metathesis reaction.
- Unsaturated aminodiols are swinging conductors and are useful as synthetic raw materials such as sphingomyelin, which are effective in drug delivery systems.
- methods for producing unsaturated aminodiols include synthesis methods using sugar as a raw material, methods using Sharpless asymmetric epoxidation, methods using Garner aldehyde, methods using asymmetric aldol reactions, and the like.
- Reported for example, Natsuo Katsumura, Toshikazu Hakogi, “Protein Nucleic Acid Enzyme”, Vol.147, No.4, 526-536 (2002)). I have bad problems, and I have a problem.
- the method for producing the unsaturated aminodiols of the present invention has the following general formula (I)
- R 1 and R 4 are a hydrogen atom or a protecting group for a hydroxyl group
- R 3 is a protecting group for a hydrogen atom or an amino group
- R 5 is a hydrogen atom or a lower alkyl group.
- the metathesis catalyst is a ruthenium carbene complex.
- the ruthenium carbene complex has the following general formula (IV):
- R 7 and R 8 are an alkyl group or an aryl group, R 9 is a phosphine ligand, and X is a halogen atom).
- unsaturated aminodiols and olefins are reacted in the presence of a metathesis catalyst. Therefore, the stereoselection is simpler, versatile and more reactive than conventional reaction steps. Because of its excellent properties (EZZ selectivity), it is possible to produce unsaturated aminodiols, which are target compounds, in high yield and yield.
- unsaturated amino diols, olefins and metathesis catalysts used in the method for producing unsaturated amino diols of the present invention are relatively inexpensive, so that unsaturated amino diols can be produced at low cost. Yes, it is possible to economically provide synthetic raw materials such as sphingomyelin that are effective for drug delivery systems. Preferred for carrying out the invention U, embodiment
- R 1 and R 4 are a hydrogen atom or a protecting group for a hydroxyl group
- R 3 is a protecting group for a hydrogen atom or an amino group
- R 5 is a hydrogen atom or a lower alkyl group.
- R is the same as defined above for R 3 , R 4 and R 6 ), and is characterized by producing an unsaturated aminodiol.
- Examples of the lower alkyl group include branched, ole, and alkenoquinole groups having 1 to 5 carbon atoms, such as a methyl group, an ethyl group, a propyl group, an isopropyl group, a petit / le group, sec- Examples include a butyl group, a t-butyl group, and a pentyl group.
- hydroxyl protecting groups include silyl protecting groups such as trimethylsilyl, triethylsilyl, t-butyldimethylsilyl, and triisopropylpropylsilyl, ether protecting groups such as methoxymethyl, tetrahydrovinylanol, and ethoxyethyl, and ester-based groups such as acetyl and benzoyl. Protecting groups can be listed.
- protecting groups for amino groups include silyl protecting groups such as trimethylsilyl, triethylsilyl, t-butyldimethylsilyl, triisopropynolesilyl, trubate protecting groups such as t, butoxycarbonyl, and benzylcarbonyl, and esters such as acetyl and benzoyl.
- System protecting groups can be opened.
- the production method of the present invention is carried out in the presence of a metathesis catalyst, and as a metathesis catalyst, a ruthenium carbene complex is preferable from the viewpoint of reaction efficiency, among the forces in which various existing metathesis catalysts are suitably used.
- ruthenium carbene complex an existing ruthenium carbene complex is preferably used, but the following general formula (IV)
- R 7 and R 8 are an anoalkyl group or an aryl group, R 9 is a phosphine ligand, and X is a halogen atom). It is preferable in terms of ease.
- the alkyl group does not participate in the reaction! /, Has a substituent! /, Mayore, carbon number
- the aryl group includes, for example, a phenyl group, a naphthyl group, a furan group, a pyrrole group, and a thiophene group, which may have a substituent not involved in the reaction .
- the phosphine ligand is a phosphine ligand substituted with the alkyl group or aryl group.
- a halogen atom is a fluorine atom, a chlorine atom, a bromine atom, or an iodine atom.
- hydrocarbon solvents such as benzene, toluene, xylene, hexane, cyclohexane, tetrahydrofuran, dimethoxyethane, dioxane, etc.
- halogenated solvents such as ether solvents, dichloromethane, chloroform, dichloroethane and the like.
- the reaction temperature is 0 ° C, and the power in the temperature range of 150 ° C can be selected as appropriate.
- the reaction speed is very economical.
- the temperature is room temperature, and the range of 80 ° C is preferred. .
- Tetrahydropyraninoreprono Gizoleate 7 Tetrahydropyranyl propargyl ether; 0.656g, 4.68mmol
- THF 29.8ml
- 1.6N hexane solution of n-butyllithium (2.80ml, 4.47mmol) was added dropwise and stirred at the same temperature for 15 minutes. One hundred of this solution. Cooled below C.
- reaction mixture was concentrated under reduced pressure, separated and purified by silica gel chromatography (9% to 25% ethyl acetate dissolved in hexane), and (2S, 3R, 4E) -2-butylene Xyloxycarbonylamino-3- (t-butyldimethylsilyloxy) -4-octadecene-1-ol (above 12) ((2S, 3R, 4E) -2-tert-Butyloxycarbonylamino-3- (tert-butyi- dimethy ⁇ silyloxy) _4-octadecene-l_ol: 12mg, 18%, E form only).
- reaction mixture was filtered, acidified with 2N hydrochloric acid, and extracted with ethyl acetate.
- the organic layer was washed successively with 2N hydrochloric acid, saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.
- reaction mixture was concentrated under reduced pressure, separated and purified by silica gel chromatography (9% to 25% ethyl acetate dissolved in hexane), and (2S, 3R, 4E)-2 -t-butylo Xyloxycarbonylamino-t-butyldimethinoresilyloxy-4-dodecene-3-ol (19 above) (71 mg, 55%) was obtained.
- IR, 3 ⁇ 4 NMR, and 13 C NMR data for (2S, 3R, 4E) -2-t-ptyloxycarboxylamino-1-1-1-butyldimethylenosilylyl-4-dodecene-3-ol are shown below. Show.
- reaction mixture was concentrated in vacuo, and purified by silica gel chromatography i (hexane to 2 0% to 33% of the acetic acid Echiru what was ⁇ to) by the separation 'Purification, (2S, 3R, 4E) - 2- 1 - Puchiruo Xyloxycarbonylamino-1-t-butyldimethylsilyloxy-14- (4 '-(7'- Nitrobenzofurazal) amino) -4-tetradecene-3-ol (21) (55 mg, 57%) was obtained.
- reaction mixture was concentrated under reduced pressure and then subjected to silica gel chromatography (17% -3% in hexane). 3% of that dissolved acetic acid Echiru) by the separation 'Purification, (2 S, 3 R, 4E) -2-t- Petit / Reokishika Ruponiruamino - 1-t-butyldimethylsilyl O carboxymethyl-4-tetradecene - 3 , 14-diol (22 above) (54 mg, 75%).
- the method for producing unsaturated aminodiols of the present invention reacts unsaturated aminodiols and olefins in the presence of a metathesis catalyst, and thus is simpler, versatile and reactive than conventional reaction steps.
- High stereoselectivity ( ⁇ / ⁇ selectivity) makes it possible to produce unsaturated aminodiols that are target compounds in high yields.
- synthetic raw materials such as sphingomyelin that are effective for drug delivery systems and the like.
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Abstract
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JP2004228054 | 2004-08-04 | ||
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JP2005024062A JP4825947B2 (ja) | 2004-08-04 | 2005-01-31 | 不飽和アミノジオール類の製造方法 |
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Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2006128657A1 (fr) * | 2005-05-31 | 2006-12-07 | Novartis Ag | Sphingolipides |
US9643915B2 (en) | 2013-03-15 | 2017-05-09 | Cerenis Therapeutics Holding Sa | Methods for the synthesis of sphingomyelins and dihydrosphingomyelins |
US9708354B2 (en) | 2013-03-15 | 2017-07-18 | Cerenis Therapeutics Holding Sa | Methods for the synthesis of sphingomyelins and dihydrosphingomyelins |
-
2005
- 2005-01-31 JP JP2005024062A patent/JP4825947B2/ja not_active Expired - Fee Related
- 2005-08-03 WO PCT/JP2005/014602 patent/WO2006014006A1/fr active Application Filing
Non-Patent Citations (3)
Title |
---|
HASEGAWA H. ET AL: "Cross Metathesis Route in Sphingomyelin Systhesis", CHEMISTRY LETTERS, vol. 33, no. 12, 5 December 2004 (2004-12-05), pages 1592 - 1593, XP002999815 * |
HASEGAWA H. ET AL: "Cross-Metathesis ni yoru Sphingo Shishitsu Goseiho", THE CHEMICAL SOCIETY OF JAPAN KOEN YOKOSHU, vol. 85, no. 2, 11 March 2005 (2005-03-11), pages 875, XP002999816 * |
TORSSELL S. ET AL: "A practical synthesis of D-erythro-sphingosine using a cross-metathesis approach", ORG.BIOMOL.CHEM., vol. 2, 7 June 2004 (2004-06-07), pages 1643 - 1646, XP008056624 * |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2006128657A1 (fr) * | 2005-05-31 | 2006-12-07 | Novartis Ag | Sphingolipides |
US9643915B2 (en) | 2013-03-15 | 2017-05-09 | Cerenis Therapeutics Holding Sa | Methods for the synthesis of sphingomyelins and dihydrosphingomyelins |
US9708354B2 (en) | 2013-03-15 | 2017-07-18 | Cerenis Therapeutics Holding Sa | Methods for the synthesis of sphingomyelins and dihydrosphingomyelins |
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JP4825947B2 (ja) | 2011-11-30 |
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