CN116120138A - 布瓦西坦的不对称催化制备方法 - Google Patents
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- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- MSYKRHVOOPPJKU-BDAKNGLRSA-N brivaracetam Chemical compound CCC[C@H]1CN([C@@H](CC)C(N)=O)C(=O)C1 MSYKRHVOOPPJKU-BDAKNGLRSA-N 0.000 title claims description 5
- 229960002161 brivaracetam Drugs 0.000 title claims description 5
- 230000003197 catalytic effect Effects 0.000 title description 3
- 238000006243 chemical reaction Methods 0.000 claims abstract description 28
- YEJRWHAVMIAJKC-UHFFFAOYSA-N 4-Butyrolactone Chemical class O=C1CCCO1 YEJRWHAVMIAJKC-UHFFFAOYSA-N 0.000 claims abstract description 24
- 238000009876 asymmetric hydrogenation reaction Methods 0.000 claims abstract description 23
- 239000003054 catalyst Substances 0.000 claims abstract description 21
- 150000001875 compounds Chemical class 0.000 claims abstract description 19
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000001257 hydrogen Substances 0.000 claims abstract description 10
- 239000010948 rhodium Substances 0.000 claims description 39
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 33
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 claims description 26
- 239000004912 1,5-cyclooctadiene Substances 0.000 claims description 24
- 125000003118 aryl group Chemical group 0.000 claims description 18
- 239000003446 ligand Substances 0.000 claims description 18
- 229910052751 metal Inorganic materials 0.000 claims description 18
- 239000002184 metal Substances 0.000 claims description 18
- 229910052786 argon Inorganic materials 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 13
- SJYNFBVQFBRSIB-UHFFFAOYSA-N norbornadiene Chemical compound C1=CC2C=CC1C2 SJYNFBVQFBRSIB-UHFFFAOYSA-N 0.000 claims description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- 229910052703 rhodium Inorganic materials 0.000 claims description 12
- 125000001072 heteroaryl group Chemical group 0.000 claims description 11
- 239000002243 precursor Substances 0.000 claims description 11
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 10
- 230000008569 process Effects 0.000 claims description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- 239000003960 organic solvent Substances 0.000 claims description 8
- 238000003786 synthesis reaction Methods 0.000 claims description 8
- 230000015572 biosynthetic process Effects 0.000 claims description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- KDUIUFJBNGTBMD-DLMDZQPMSA-N [8]annulene Chemical compound C/1=C/C=C\C=C/C=C\1 KDUIUFJBNGTBMD-DLMDZQPMSA-N 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 claims description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 4
- 239000005977 Ethylene Substances 0.000 claims description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
- 229910018286 SbF 6 Inorganic materials 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- 239000000654 additive Substances 0.000 claims description 4
- 239000012298 atmosphere Substances 0.000 claims description 4
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 claims description 4
- 230000000536 complexating effect Effects 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 3
- VYXHVRARDIDEHS-UHFFFAOYSA-N 1,5-cyclooctadiene Chemical compound C1CC=CCCC=C1 VYXHVRARDIDEHS-UHFFFAOYSA-N 0.000 claims description 3
- 230000000996 additive effect Effects 0.000 claims description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 2
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 2
- CZKMPDNXOGQMFW-UHFFFAOYSA-N chloro(triethyl)germane Chemical compound CC[Ge](Cl)(CC)CC CZKMPDNXOGQMFW-UHFFFAOYSA-N 0.000 claims description 2
- 238000005984 hydrogenation reaction Methods 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 238000011065 in-situ storage Methods 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims description 2
- 239000005051 trimethylchlorosilane Substances 0.000 claims description 2
- 239000012450 pharmaceutical intermediate Substances 0.000 claims 1
- GOUILHYTHSOMQJ-UHFFFAOYSA-N gamma-butenolide Natural products CCC1OC(=O)C=C1 GOUILHYTHSOMQJ-UHFFFAOYSA-N 0.000 abstract description 14
- 230000003287 optical effect Effects 0.000 abstract description 3
- 238000009776 industrial production Methods 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 14
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 235000019439 ethyl acetate Nutrition 0.000 description 5
- 238000003818 flash chromatography Methods 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 4
- PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 description 4
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- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical group [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 3
- 239000012300 argon atmosphere Substances 0.000 description 3
- 239000012018 catalyst precursor Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Substances C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 239000004305 biphenyl Substances 0.000 description 2
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- 229940125890 compound Ia Drugs 0.000 description 2
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- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- -1 n-octyl Chemical group 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 229940049954 penicillin Drugs 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 2
- HNNJFUDLLWOVKZ-VKHMYHEASA-N (2s)-2-aminobutanamide Chemical compound CC[C@H](N)C(N)=O HNNJFUDLLWOVKZ-VKHMYHEASA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 238000006683 Mannich reaction Methods 0.000 description 1
- 238000007259 addition reaction Methods 0.000 description 1
- 238000005575 aldol reaction Methods 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
- 238000006254 arylation reaction Methods 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
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- 208000012839 conversion disease Diseases 0.000 description 1
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- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
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- 230000004048 modification Effects 0.000 description 1
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- 125000000896 monocarboxylic acid group Chemical group 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
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000013341 scale-up Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
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- 239000002904 solvent Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 238000010189 synthetic method Methods 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B53/00—Asymmetric syntheses
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- 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
- B01J31/2282—Unsaturated compounds used as ligands
- B01J31/2295—Cyclic compounds, e.g. cyclopentadienyls
-
- 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
- B01J31/24—Phosphines, i.e. phosphorus bonded to only carbon atoms, or to both carbon and hydrogen atoms, including e.g. sp2-hybridised phosphorus compounds such as phosphabenzene, phosphole or anionic phospholide ligands
- B01J31/2404—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring
- B01J31/2409—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring with more than one complexing phosphine-P atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
- C07D207/263—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms
- C07D207/27—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/26—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D307/30—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/32—Oxygen atoms
- C07D307/33—Oxygen atoms in position 2, the oxygen atom being in its keto or unsubstituted enol form
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- B—PERFORMING OPERATIONS; TRANSPORTING
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- 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
- B01J2231/60—Reduction reactions, e.g. hydrogenation
- B01J2231/64—Reductions in general of organic substrates, e.g. hydride reductions or hydrogenations
- B01J2231/641—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes
- B01J2231/645—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes of C=C or C-C triple bonds
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- 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
- B01J2531/822—Rhodium
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- B—PERFORMING OPERATIONS; TRANSPORTING
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- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/80—Complexes comprising metals of Group VIII as the central metal
- B01J2531/84—Metals of the iron group
- B01J2531/842—Iron
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- C—CHEMISTRY; METALLURGY
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
本发明公开了一种γ‑丁内酯衍生物的不对称氢化制备方法,该方法采用廉价易得的氢气为氢源,通过手性Rh催化剂催化的γ‑丁烯酸内酯衍生物不对称氢化反应来制备γ‑丁内酯衍生物。本发明具有的优点在于反应收率高,成本低,制备的手性化合物光学纯度高,操作简单易行,易于工业化生产等。
Description
技术领域
本发明属于化学合成技术领域,涉及到一种γ-丁内酯衍生物的制备方法。
背景技术
γ-丁内酯是一种广泛存在于天然产物和药物分子中的核心骨架结构。具有光学活性的γ-丁内酯可以作为一大类重要的手性结构单元来合成多种高生物活性化合物和复杂分子。针对研究如何高对映选择性的合成γ-丁内酯衍生物在有机化学和医药和医药合成工业都具有十分重要的意义,同时也为发展具有新型生理学活性的药物分子提供高效的合成工具。因此,γ-丁内酯衍生物的对映选择性合成方法已经被大量的开发出来。而γ-丁烯酸内酯衍生物作为一种廉价易得的化学原料,关于如何将γ-丁烯酸内酯通过高效的不对称合成反应转化为具有光学活性的γ-丁内酯衍生物也因此成为该领域的研究重点,例如γ-丁烯酸内酯衍生物的不对称Aldol反应、不对称Mannich反应、不对称芳基化/烷基化反应、不对称1,4-加成反应、不对称烯丙基取代反应、不对称环加成反应、不对称还原反应等。其中,γ-丁烯酸内酯的不对称氢化凭借其在工业合成中的巨大应用潜力获得了广泛的研究关注度。
文献J.Org.Chem.1995,60,357-363首次报道了Ru/BINAP催化剂催化的γ-丁烯酸内酯的不对称氢化反应。虽然该反应的转化率高,但是反应条件苛刻,对映选择性很差。
文献Chem.Eur.J.2012,18,6507-6513报道了金属Ir催化剂催化的γ-丁烯酸内酯的不对称氢化反应。该反应使用了较为廉价的Ir金属,但是反应活性差,不对称氢化转化率很低。
现有技术中,存在催化剂活性差,反应转化数低,反应时间长,制备成本高昂等一系列问题。因此,发展一种催化效率高,对映选择性好的金属催化剂体系来制备γ-丁烯酸内酯的方法具有重要意义。
发明内容
定义
为便于对本发明的理解,除非另外说明的,对本文使用的一些术语、缩写或其它缩略语定义如下。
“烷基”,单用或与其它基团合用时,代表含1~8个碳原子的饱和直链或支链基团,例如:甲基、乙基、正丙基、异丙基、正丁基、仲丁基、叔丁基、戊基、正戊基、正己基、异己基、正庚基、正辛基和正癸基等。
“芳基”,单用或与其它基团合用时,指含有1、2或3个环的任选取代的芳香碳环基团,所述环之间以键连或稠合方式连接,例如:苯基、联苯基、萘基、四氢化萘、二氢化茚,其可进一步被其它芳基或含芳基的取代基取代。
“杂芳基”,单用或与其它基团合用时,指含有1或2个环的任选取代的芳香杂环基团,所述杂环上的杂原子为1~3个,相同或不同,选自O、N、S,例如:苯基、联苯基、萘基、四氢化萘、二氢化茚,其可进一步被其它芳基或含芳基的取代基取代。
COD表示1,5-环辛二烯。
COT表示环辛四烯。
NBD表示降冰片二烯。
TMSI表示三甲基碘硅烷。
发明详述
为了克服现有技术的不足,本发明的目的在于提供γ-丁内酯衍生物的不对称氢化制备方法,该方法以手性的铑(I)-配体络合物为催化剂,以氢气作氢源,能够在温和的条件下实现布瓦西坦的手性制备,具有配体廉价易得,反应简洁,收率高、对映选择性好、成本低、绿色环保等优点。
本发明是通过以下技术方案实行的。
γ-丁内酯衍生物的不对称氢化制备方法,包括式(Ⅰ)化合物在铑(I)催化剂的存在下,于氢气氛和有机溶剂中反应,生成式(Ⅱ)所示化合物,
其中,化合物式(Ⅰ)和式(ⅠI)中的R1和R2基团为烷基、芳基、芳基烷基,R3基团为氢和羟基,“*”表示手性立体构型;
所述铑(I)催化剂由铑金属前体和配体混合后生成;
所述配体具有如下式(Ⅲ)所示的结构,
其中,
R为H、D、CF3或C1~C3烷基;
Ar为芳基或杂芳基,其中,各芳基、杂芳基分别任选地被一个或多个独立选自D、F、Cl、Br、I、CN、NO2、CF3、C1-C4烷基、C1-C4烷氧基的基团所取代。
在一些实施例中,R为H、D、CF3、甲基、乙基或异丙基;
且/或,Ar为芳基或杂芳基,其中,各芳基、杂芳基分别任选地被1个或多个独立选自D、F、Cl、Br、I、CN、NO2、CF3、甲基、乙基、甲氧基的基团所取代;
且/或,所述芳基、杂芳基上的取代基为1个、2个、3个或5个。
在一些实施例中,所述配体选自具有以下R和Ar基团组合的化合物Ⅲa~Ⅲj,
Ⅲa:R=H,Ar=Ph;
Ⅲb:R=Me,Ar=Ph;
Ⅲc:R=H,Ar=p-Me-Ph;
Ⅲd:R=H,Ar=p-MeO-Ph;
Ⅲe:R=H,Ar=3,5-di-Me-Ph;
Ⅲf:R=H,Ar=3,5-di-Me-4-MeO-Ph;
Ⅲg:R=H,Ar=3,5-di-MeO-Ph;
Ⅲh:R=H,Ar=3,5-di-MeO-4-Me-Ph;
Ⅲi:R=H,Ar=3,4,5-tri-MeO-Ph;
Ⅲj:R=Me,Ar=3,4,5-tri-Me-Ph。
在一些实施例中,所述铑金属前体为具有通式RhY1Y2X或RhY1Z1Z2X的铑(I)络合物或具有通式[RhY1X]2或[RhZ1Z2X]2的二聚铑(I)络合物,其中,Y1、Y2独立地为降冰片二烯NBD、1,5-环辛二烯COD、环辛四烯COT,Z1、Z2独立地为乙烯或PPh3,X为F、Cl、Br、I、OH、BF4、SbF6、OTf、PF6或PPh2;
且/或,述铑(I)催化剂相对于式(I)化合物的摩尔百分比为0.01%~1%。
在一些实施例中,所述的手性Rh金属催化剂中金属选自Rh(NBD)2BF4、Rh(COD)2BF4、Rh(COD)2Cl、Rh(COD)2SbF6、Rh(COD)2OTf、[Rh(COD)(PPh3)2]BF4、[Rh(NBD)Cl]2、[Rh(COD)BF4]2、[Rh(COD)Cl]2、[Rh(乙烯)2Cl]2、[Rh(COD)PF6]2和[Rh(COD)OH]2中一种或多种的混合。
在一些实施例中,所述铑(I)催化剂由铑金属前体和配体在有机溶剂中预先络合生成,或者,所述铑(I)催化剂由铑金属前体和配体在反应体系中混合后原位络合生成;
且/或,所述配体选自Ⅲa~Ⅲj;
且/或,所述铑(I)催化剂相对于式(I)化合物的摩尔百分比为0.01%~1%,优选为优选为0.05%-0.1%;
且/或,所述铑金属前体与配体的投料比为1:1~1:1.2。
在一些实施例中,所述有机溶剂选自氯仿、二氯甲烷、1,2-二氯乙烷、异丙醇、乙醇、甲醇、三氟乙醇、1,4-二氧六环、四氢呋喃、乙腈中的一种或多种的混合;且/或,式(I)化合物与有机溶剂的摩尔体积比(mol/L)为1:1~1:100;
且/或,所述反应的温度为10-60℃,优选30℃~40℃;
且/或,所述氢气氛的压力为1-9Mpa,优选4Mpa~6Mpa。
在一些实施例中,所述的氢化反应的添加剂选自三氟乙酸,乙酸,磷酸,盐酸,硫酸,三氟化硼乙醚,三氟甲烷磺酸银,三甲硅烷基三氟甲磺酸酯,三甲基氯硅烷,优选为三氟乙酸。
上述技术方案中的一个技术方案具有如下优点或有益效果:通过手性金属催化剂并筛选最优手性配体,对γ-丁烯酸内酯I进行不对称氢化反应,即可以高光学纯度、高收率的来制备γ-丁内酯衍生物II,并且反应条件温和,适合业放大生产。合成操作简单,总收率高,立体选择性好,具有巨大的工业应用前景。
具体实施方式
为了使本发明易于理解,结合具体实施例对本发明做进一步的说明。
实施例中未注明具体条件的实验方法,通常按照常规条件以及手册中所述的条件,或按照制造厂商所建议的条件;所用材料、试剂等,如无特殊说明,均可从商业途径得到。
实施例1:由γ-丁烯酸内酯Ia的不对称氢化反应制备γ-丁内酯衍生物IIa
在氩气氛围的手套箱中,向10mL西林瓶中加入催化剂前体Rh(NBD)2BF4(3.7mg,1.0×10-2mmol)、Zhaophos(9.5mg,1.1×10-2mmol)和无水DCM(2.0mL)。室温下,将混合物搅拌2h。加入化合物Ia(0.16g,1.0mmol)后,将西林瓶放置在高压釜中,关闭高压釜后将其从手套箱中取出。高压釜快速用氢气置换3次,然后加压至50atm H2。反应液在室温下搅拌24小时,然后小心释放气压。减压除去DCM后,将反应混合物用硅胶快速色谱法纯化(流动相石油醚:乙酸乙酯=3:1)得到白色固体化合物IIa,产率98%,98%ee。对映比ee通过HPLC测定:Daicel Chiralpak AS-3 column(0.46x25cm),Hexane/iPrOH=85:15,flow rate=1.0mL/min,λ=210nm,tR:17.730min(major),19.896min(minor)。
MS(m/z):[M+H]+=163.07
1H NMR(600MHz,CDCl3)δ7.39–7.35(m,2H),7.30(dd,J=7.2,7.2Hz,1H),7.25–7.21(m,2H),4.69–4.64(m,1H),4.29–4.25(m,1H),3.79(p,J=8.4Hz,1H),2.92(dd,J=17.5,8.8Hz,1H),2.68(dd,J=17.5,9.1Hz,1H)ppm;13C NMR(150MHz,CDCl3)δ176.5,139.5,129.2,127.8,126.8,74.1,41.2,35.8ppm.
实施例2:由γ-丁烯酸内酯Ia'的不对称氢化反应制备γ-丁内酯衍生物IIa
在氩气氛围的手套箱中,向10mL西林瓶中加入催化剂前体Rh(NBD)2BF4(3.7mg,1.0×10-2mmol)、Zhaophos(9.5mg,1.1×10-2mmol)和无水DCM(2.0mL)。室温下,将混合物搅拌2h。加入化合物Ia'(0.18g,1.0mmol)和三氟乙酸(11.4mg,0.1mmol)后,将西林瓶放置在高压釜中,关闭高压釜后将其从手套箱中取出。高压釜快速用氢气置换3次,然后加压至50atmH2。反应液在室温下搅拌24小时,然后小心释放气压。减压除去DCM后,将反应混合物用硅胶快速色谱法纯化(流动相石油醚:乙酸乙酯=3:1)得到白色固体化合物IIa,产率98%,96%ee。对映比ee通过HPLC测定:Daicel Chiralpak AS-3column(0.46x25cm),Hexane/iPrOH=85:15,flow rate=1.0mL/min,λ=210nm,tR:17.730min(major),19.896min(minor)。
实施例3:γ-丁烯酸内酯Ia不对称氢化反应的金属前体和配体优化
a转化率和对映比(ee)由HPLC测定
实施例4:γ-丁烯酸内酯Ia不对称氢化反应溶剂筛选
Entry | Solvent | <![CDATA[Conversion<sup>a</sup>(%)]]> | <![CDATA[ee<sup>a</sup>(%)]]> |
1 | DCM | 100 | 98 |
2 | DCE | 25 | 96 |
3 | MeOH | 29 | 96 |
4 | EtOH | 19 | 97 |
5 | <![CDATA[CF<sub>3</sub>CH<sub>2</sub>OH]]> | 59 | 98 |
6 | EtOAc | 100 | 97 |
7 | toluene | 91 | 95 |
8 | THF | 79 | 97 |
9 | 1,4-dioxane | 30 | 16 |
a转化率和对映比(ee)由HPLC测定
实施例5:γ-丁烯酸内酯Ia’不对称氢化反应添加剂筛选
a转化率和对映比(ee)由HPLC测定
实施例6:γ-丁烯酸内酯不对称氢化反应的底物拓展
a转化率和对映比(ee)由HPLC测定b分离收率(快速柱层析纯化,流动相石油醚/乙酸乙酯=5:1)c加入添加剂CF3COOH(10mol%)
实施例7:布瓦西坦的合成
在氩气氛围的手套箱中,向西林瓶中加入催化剂前体Rh(NBD)2BF4(3.7mg,10μmol)、Zhaophos(9.7mg,11μmol)和无水DCM(1.0mL)。室温下,将混合物搅拌2h。反应瓶中加入化合物In(1.26g,10mmol溶解于10mL DCM)和三氟乙酸(11.4mg,0.1mmol)后,转移西林瓶中催化剂溶液(0.2mL)至反应瓶中,然后将反应瓶放置在高压釜中,关闭高压釜后将其从手套箱中取出。高压釜快速用氢气置换3次,然后加压至50atm H2。反应液在室温下搅拌24小时,然后小心释放气压。减压除去DCM后,将反应混合物用硅胶快速色谱法纯化(流动相:石油醚:乙酸乙酯=3:1)得到无色液体化合物IIn(1.3g),产率98%,95%ee。
向50mL圆底瓶中加入化合物IIn(0.77g,6.0mmol)和无水DCM(20mL)。将溶液降温至0℃后,加入TMSI(1.3mL,9.0mmol),0℃下搅拌1小时。加入1M HCl(30mL),水相用DCM萃取三次(3×20mL),合并有机相后用水洗(30mL),饱和食盐水洗(30mL),用无水硫酸镁干燥,浓缩至干得到黄色液体粗产品(1.7g)。
室温下,将上述粗产品重新溶解到无水DCM(30mL)中,加入两滴DMF后冷却至0℃。将草酰氯(0.78mL,9.0mmol)缓慢滴加到反应液中后,将反应温度升至室温,并继续搅拌5小时。将反应液浓缩至干后,得到棕红色液体粗产品(1.6g)。室温下,将该粗产品重新溶解到无水甲苯(20mL)中,加入(S)-(+)-2-氨基丁酰胺(0.67g,6.6mmol)和N,N-二异丙基乙基胺(1.6g,12mmol)。加热反应液至90℃,搅拌过夜。冷却至室温后,加入水(50mL)。分层后,水相用DCM萃取三次(3×20mL),合并有机相后用水洗(30mL),饱和食盐水洗(30mL),用无水硫酸镁干燥,浓缩至干。得到的粗产品用硅胶快速色谱法纯化(流动相二氯甲烷:甲醇=95:5)得到白色固体化合物V(0.87g),三步总产率68%,96.9:3.1dr,>99%ee。[α]D 23=–57.8(c1.0,CHCl3);1H NMR(600MHz,CDCl3)δ[ppm]=6.31(s,1H),5.56(s,1H),4.44(dd,J=8.8,6.8Hz,1H),3.48(dd,J=9.8,7.9Hz,1H),3.02(dd,J=9.8,7.1Hz,1H),2.57(dd,J=16.8,8.7Hz,1H),2.32(hept,J=7.7Hz,1H),2.07(dd,J=16.8,8.0Hz,1H),1.93(dp,J=14.4,7.3Hz,1H),1.68(dp,J=14.9,7.5Hz,1H),1.40(q,J=7.4Hz,2H),1.36–1.27(m,2H),0.90(q,J=7.1Hz,6H);13C NMR(150MHz,CDCl3)δ[ppm]=175.8,172.2,56.1,49.7,38.0,36.7,32.0,21.0,20.7,14.1,10.6;ee值通过HPLC测定:Chiracel IC-3column(0.46x25cm),n-hexane/i-propanol=45:55,flow rate=1.0mL/min,λ=210nm,tR:10.619min(2S,4R)(major),15.755min(2S,4S)(minor).
以上所述实施例仅代表了本发明的优选实施方式,需要指出的是,对于本技术工艺领域的技术人员,在利用本发明的构思与方法所作出的改进与润饰,同样应当视为在本发明的保护范围之内。
Claims (10)
2.根据权利要求1所述γ-丁内酯衍生物的不对称氢化制备方法,其特征在于:
R为H、D、CF3、甲基、乙基或异丙基;
且/或,Ar为芳基或杂芳基,其中,各芳基、杂芳基分别任选地被1个或多个独立选自D、F、Cl、Br、I、CN、NO2、CF3、甲基、乙基、甲氧基的基团所取代;
且/或,所述芳基、杂芳基上的取代基为1个、2个、3个或5个。
3.根据权利要求1所述γ-丁内酯衍生物的不对称氢化制备方法,其特征在于,所述配体选自具有以下R和Ar基团组合的化合物Ⅲa~Ⅲj,
Ⅲa:R=H,Ar=Ph;
Ⅲb:R=Me,Ar=Ph;
Ⅲc:R=H,Ar=p-Me-Ph;
Ⅲd:R=H,Ar=p-MeO-Ph;
Ⅲe:R=H,Ar=3,5-di-Me-Ph;
Ⅲf:R=H,Ar=3,5-di-Me-4-MeO-Ph;
Ⅲg:R=H,Ar=3,5-di-MeO-Ph;
Ⅲh:R=H,Ar=3,5-di-MeO-4-Me-Ph;
Ⅲi:R=H,Ar=3,4,5-tri-MeO-Ph;
Ⅲj:R=Me,Ar=3,4,5-tri-Me-Ph。
4.根据权利要求1所述的γ-丁内酯衍生物的不对称氢化制备方法,其特征在于,所述铑金属前体为具有通式RhY1Y2X或RhY1Z1Z2X的铑(I)络合物或具有通式[RhY1X]2或[RhZ1Z2X]2的二聚铑(I)络合物,其中,Y1、Y2独立地为降冰片二烯NBD、1,5-环辛二烯COD、环辛四烯COT,Z1、Z2独立地为乙烯或PPh3,X为F、Cl、Br、I、OH、BF4、SbF6、OTf、PF6或PPh2;
且/或,述铑(I)催化剂相对于式(I)化合物的摩尔百分比为0.01%~1%。
5.根据权利要求4所述的方法,其特征在于,所述的手性Rh金属催化剂中金属选自Rh(NBD)2BF4、Rh(COD)2BF4、Rh(COD)2Cl、Rh(COD)2SbF6、Rh(COD)2OTf、[Rh(COD)(PPh3)2]BF4、[Rh(NBD)Cl]2、[Rh(COD)BF4]2、[Rh(COD)Cl]2、[Rh(乙烯)2Cl]2、[Rh(COD)PF6]2和[Rh(COD)OH]2中一种或多种的混合。
6.根据权利要求1至5任一项所述的γ-丁内酯衍生物的不对称氢化制备方法,其特征在于,
所述铑(I)催化剂由铑金属前体和配体在有机溶剂中预先络合生成,或者,所述铑(I)催化剂由铑金属前体和配体在反应体系中混合后原位络合生成;
且/或,所述配体选自Ⅲa~Ⅲj;
且/或,所述铑(I)催化剂相对于式(I)化合物的摩尔百分比为0.01%~1%;
且/或,所述铑金属前体与配体的投料比为1:1~1:1.2。
7.根据权利要求1至5任一项所述的γ-丁内酯衍生物的不对称氢化制备方法,其特征在于,
所述有机溶剂选自氯仿、二氯甲烷、1,2-二氯乙烷、异丙醇、乙醇、甲醇、三氟乙醇、1,4-二氧六环、四氢呋喃、乙腈中的一种或多种的混合;且/或,式(I)化合物与有机溶剂的摩尔体积比(mol/L)为1:1~1:100;
且/或,所述反应的温度为10-60℃;
且/或,所述氢气氛的压力为1-9Mpa。
8.如权利要求1所述的γ-丁内酯衍生物的不对称氢化制备方法,其特征在于,所述的氢化反应的添加剂选自三氟乙酸,乙酸,磷酸,盐酸,硫酸,三氟化硼乙醚,三氟甲烷磺酸银,三甲硅烷基三氟甲磺酸酯,三甲基氯硅烷。
9.由权利要求1至9任一项所述制备方法制得的γ-丁内酯衍生物。
10.如权利要求1至9所述的γ-丁内酯衍生物的不对称氢化制备方法,其特征在于,可应用于布立西坦药物中间体IIn和布立西坦I的合成。
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Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1997007111A1 (de) * | 1995-08-19 | 1997-02-27 | Basf Aktiengesellschaft | Verfahren zur herstellung von butyrolactonen |
WO2014203963A1 (ja) * | 2013-06-20 | 2014-12-24 | 株式会社クラレ | 3座アミノジカルベン配位子を有する金属錯体及びそれを用いた水素化還元方法 |
CN105646319A (zh) * | 2015-12-30 | 2016-06-08 | 佛山市隆信医药科技有限公司 | 一种布瓦西坦的制备方法 |
CN107721896A (zh) * | 2017-10-19 | 2018-02-23 | 丽珠集团新北江制药股份有限公司 | 一种布瓦西坦的中间体的制备方法 |
CN115181081A (zh) * | 2022-08-17 | 2022-10-14 | 青岛科技大学 | 一种β-苯基-γ-丁内酯的合成方法 |
-
2023
- 2023-01-30 CN CN202310108323.1A patent/CN116120138A/zh active Pending
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1997007111A1 (de) * | 1995-08-19 | 1997-02-27 | Basf Aktiengesellschaft | Verfahren zur herstellung von butyrolactonen |
WO2014203963A1 (ja) * | 2013-06-20 | 2014-12-24 | 株式会社クラレ | 3座アミノジカルベン配位子を有する金属錯体及びそれを用いた水素化還元方法 |
CN105646319A (zh) * | 2015-12-30 | 2016-06-08 | 佛山市隆信医药科技有限公司 | 一种布瓦西坦的制备方法 |
CN107721896A (zh) * | 2017-10-19 | 2018-02-23 | 丽珠集团新北江制药股份有限公司 | 一种布瓦西坦的中间体的制备方法 |
CN115181081A (zh) * | 2022-08-17 | 2022-10-14 | 青岛科技大学 | 一种β-苯基-γ-丁内酯的合成方法 |
Non-Patent Citations (4)
Title |
---|
QIWEI LANG等: "Highlly enantioselective synthesis of chiral γ-lactams by Rh-catalyzed asymmetric hydrogenation", 《ACS CATALYSIS》, vol. 8, 23 April 2018 (2018-04-23), pages 18 - 26 * |
姜麟忠: "《催化氢化在有机合成中的应用》", 30 September 1987, 化学工业出版社, pages: 266 - 267 * |
孟繁浩: "《药物化学》", 31 July 2021, 中国医药科学技术出版社, pages: 358 * |
钟邦克: "《精细化工过程催化作用》", 31 August 2002, 中国石化出版社, pages: 62 * |
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