JP4617457B2 - Method for producing racemic octahydrobisisoquinoline, method for producing optically active octahydrobisisoquinoline and optically active octahydrobisisoquinoline - Google Patents
Method for producing racemic octahydrobisisoquinoline, method for producing optically active octahydrobisisoquinoline and optically active octahydrobisisoquinoline Download PDFInfo
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- JP4617457B2 JP4617457B2 JP2004011109A JP2004011109A JP4617457B2 JP 4617457 B2 JP4617457 B2 JP 4617457B2 JP 2004011109 A JP2004011109 A JP 2004011109A JP 2004011109 A JP2004011109 A JP 2004011109A JP 4617457 B2 JP4617457 B2 JP 4617457B2
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- octahydrobisisoquinoline
- racemic
- optically active
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- bisisoquinoline
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- 238000004519 manufacturing process Methods 0.000 title claims description 16
- 238000006243 chemical reaction Methods 0.000 claims description 18
- 230000003287 optical effect Effects 0.000 claims description 14
- 150000002821 niobium Chemical class 0.000 claims description 11
- IOEPOEDBBPRAEI-UHFFFAOYSA-N 1,2-dihydroisoquinoline Chemical compound C1=CC=C2CNC=CC2=C1 IOEPOEDBBPRAEI-UHFFFAOYSA-N 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 9
- 239000003638 chemical reducing agent Substances 0.000 claims description 7
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 6
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 6
- 229910052725 zinc Inorganic materials 0.000 claims description 6
- 239000011701 zinc Substances 0.000 claims description 6
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 5
- 239000011777 magnesium Substances 0.000 claims description 5
- 229910052749 magnesium Inorganic materials 0.000 claims description 5
- 229910052758 niobium Inorganic materials 0.000 claims description 4
- 239000010955 niobium Substances 0.000 claims description 4
- GUCVJGMIXFAOAE-UHFFFAOYSA-N niobium atom Chemical compound [Nb] GUCVJGMIXFAOAE-UHFFFAOYSA-N 0.000 claims description 4
- 229910052742 iron Inorganic materials 0.000 claims description 3
- 239000012280 lithium aluminium hydride Substances 0.000 claims description 3
- -1 lithium aluminum hydride Chemical compound 0.000 claims description 3
- 229960002510 mandelic acid Drugs 0.000 claims description 3
- 239000012279 sodium borohydride Substances 0.000 claims description 3
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 3
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 claims 1
- 150000001735 carboxylic acids Chemical class 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- 239000007787 solid Substances 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 238000005859 coupling reaction Methods 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- 239000003054 catalyst Substances 0.000 description 8
- 239000013078 crystal Substances 0.000 description 8
- 150000002736 metal compounds Chemical class 0.000 description 8
- 239000012046 mixed solvent Substances 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 238000010168 coupling process Methods 0.000 description 6
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 230000008878 coupling Effects 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 235000002597 Solanum melongena Nutrition 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 150000004780 naphthols Chemical class 0.000 description 4
- 230000035484 reaction time Effects 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 150000004786 2-naphthols Chemical class 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- YHBDIEWMOMLKOO-UHFFFAOYSA-I pentachloroniobium Chemical compound Cl[Nb](Cl)(Cl)(Cl)Cl YHBDIEWMOMLKOO-UHFFFAOYSA-I 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 2
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- NKSZCPBUWGZONP-UHFFFAOYSA-N 3,4-dihydroisoquinoline Chemical compound C1=CC=C2C=NCCC2=C1 NKSZCPBUWGZONP-UHFFFAOYSA-N 0.000 description 2
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 239000003905 agrochemical Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 239000007810 chemical reaction solvent Substances 0.000 description 2
- 150000001879 copper Chemical class 0.000 description 2
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- YVVBECLPRBAATK-UHFFFAOYSA-N methyl 3-hydroxynaphthalene-2-carboxylate Chemical compound C1=CC=C2C=C(O)C(C(=O)OC)=CC2=C1 YVVBECLPRBAATK-UHFFFAOYSA-N 0.000 description 2
- 150000003009 phosphonic acids Chemical class 0.000 description 2
- 230000003595 spectral effect Effects 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
- PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 1
- SEZHLKZEWYFCRB-UHFFFAOYSA-N 1,2-dimethoxyethane;oxolane Chemical compound C1CCOC1.COCCOC SEZHLKZEWYFCRB-UHFFFAOYSA-N 0.000 description 1
- 102100027324 2-hydroxyacyl-CoA lyase 1 Human genes 0.000 description 1
- SCOGIYZPQMECLW-UHFFFAOYSA-N COC(c1cc(cccc2)c2c(-c2c(cccc3)c3cc(C(OC)=O)c2O)c1O)=O Chemical compound COC(c1cc(cccc2)c2c(-c2c(cccc3)c3cc(C(OC)=O)c2O)c1O)=O SCOGIYZPQMECLW-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical group [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
- 101001009252 Homo sapiens 2-hydroxyacyl-CoA lyase 1 Proteins 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- ODWXUNBKCRECNW-UHFFFAOYSA-M bromocopper(1+) Chemical compound Br[Cu+] ODWXUNBKCRECNW-UHFFFAOYSA-M 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- SBTSVTLGWRLWOD-UHFFFAOYSA-L copper(ii) triflate Chemical compound [Cu+2].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F SBTSVTLGWRLWOD-UHFFFAOYSA-L 0.000 description 1
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- DSYRJFDOOSKABR-UHFFFAOYSA-I niobium(v) bromide Chemical compound [Br-].[Br-].[Br-].[Br-].[Br-].[Nb+5] DSYRJFDOOSKABR-UHFFFAOYSA-I 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- FWIYBTVHGYLSAZ-UHFFFAOYSA-I pentaiodoniobium Chemical compound I[Nb](I)(I)(I)I FWIYBTVHGYLSAZ-UHFFFAOYSA-I 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- XOJVVFBFDXDTEG-UHFFFAOYSA-N pristane Chemical compound CC(C)CCCC(C)CCCC(C)CCCC(C)C XOJVVFBFDXDTEG-UHFFFAOYSA-N 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 150000003681 vanadium Chemical class 0.000 description 1
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- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Description
本発明は、ラセミ体オクタヒドロビスイソキノリンの製造方法及び光学活性オクタヒドロビスイソキノリンの製造方法並びに光学活性オクタヒドロビスイソキノリンに関する。 The present invention relates to a method for producing racemic octahydrobisisoquinoline, a method for producing optically active octahydrobisisoquinoline, and an optically active octahydrobisisoquinoline.
従来、ジヒドロイソキノリンを、亜鉛、クロロトリメチルシラン(TMSCl)及び1,2−ジブロモエタンを触媒として二量化してオクタヒドロビスイソキノリンを得ることが知られている(非特許文献1参照)。 Conventionally, it is known that dihydroisoquinoline is dimerized using zinc, chlorotrimethylsilane (TMSCl) and 1,2-dibromoethane as catalysts to obtain octahydrobisisoquinoline (see Non-Patent Document 1).
従来の反応では、オクタヒドロビスイソキノリンのラセミ体とメソ体とがほぼ1:1で生成するが、ラセミ体を選択的に合成する方法は知られていない。 In the conventional reaction, a racemic form and a meso form of octahydrobisisoquinoline are produced in a ratio of about 1: 1, but a method for selectively synthesizing the racemic form is not known.
本発明は、上述した事情に鑑み、オクタヒドロビスイソキノリンのラセミ体を優位に合成する方法及びそれを光学分割して(+)−又は(−)−オクタヒドロビスイソキノリンを得る方法並びにそれにより得られた(+)−又は(−)−オクタヒドロビスイソキノリンを提供することを課題とする。 In view of the above-described circumstances, the present invention provides a method for preferentially synthesizing a racemate of octahydrobisisoquinoline, a method for optically resolving it to obtain (+)-or (-)-octahydrobisisoquinoline, and a method obtained thereby It is an object of the present invention to provide (+)-or (-)-octahydrobisisoquinoline obtained.
前記課題を解決する本発明の第1の態様は、ジヒドロイソキノリンを二量化してオクタヒドロビスイソキノリンを得るに際し、ニオビウム塩を反応促進剤として用いることによりラセミ体オクタヒドロビスイソキノリンを得ることを特徴とするラセミ体オクタヒドロビスイソキノリンの製造方法にある。 The first aspect of the present invention for solving the above-mentioned problems is characterized in that when dihydroisoquinoline is dimerized to obtain octahydrobisisoquinoline, a racemic octahydrobisisoquinoline is obtained by using a niobium salt as a reaction accelerator. In the production method of racemic octahydrobisisoquinoline.
本発明の第2の態様は、第1の態様において、前記ニオビウム塩と共に当該ニオビウムを還元する還元剤を用いることを特徴とするラセミ体オクタヒドロビスイソキノリンの製造方法にある。 According to a second aspect of the present invention, there is provided a method for producing racemic octahydrobisisoquinoline according to the first aspect, wherein a reducing agent for reducing the niobium is used together with the niobium salt.
本発明の第3の態様は、第2の態様において、前記還元剤が、亜鉛、マグネシウム、鉄、水素化アルミニウムリチウム、水素化ホウ素ナトリウムからなる群から選択される少なくとも一種であることを特徴とするラセミ体オクタヒドロビスイソキノリンの製造方法にある。 According to a third aspect of the present invention, in the second aspect, the reducing agent is at least one selected from the group consisting of zinc, magnesium, iron, lithium aluminum hydride, and sodium borohydride. A method for producing racemic octahydrobisisoquinoline.
本発明の第4の態様は、第1〜3の何れかの態様の方法で得られたラセミ体オクタヒドロビスイソキノリンを光学分割することにより(+)−及び(−)−オクタヒドロビスイソキノリンの少なくとも一方を得ることを特徴とする光学活性オクタヒドロビスイソキノリンの製造方法にある。 According to a fourth aspect of the present invention, (+)-and (-)-octahydrobisisoquinoline is obtained by optical resolution of racemic octahydrobisisoquinoline obtained by the method of any one of the first to third aspects. It is in a method for producing optically active octahydrobisisoquinoline characterized in that at least one is obtained.
本発明の第5の態様は、第4の態様において、前記光学分割を、(d)−及び(l)−カンファースルホン酸、(d)−及び(l)−マンデル酸、光学活性カルボン酸及び光学活性ホスホン酸からなる群から選択される少なくとも一種を用いて行うことを特徴とする光学活性オクタヒドロビスイソキノリンの製造方法にある。 According to a fifth aspect of the present invention, in the fourth aspect, the optical resolution is performed by (d)-and (l) -camphorsulfonic acid, (d)-and (l) -mandelic acid, optically active carboxylic acid and The present invention relates to a method for producing optically active octahydrobisisoquinoline, which is carried out using at least one selected from the group consisting of optically active phosphonic acids.
本発明の第6の態様は、不斉カップリングの触媒として機能し、(+)−オクタヒドロビスイソキノリンからなることを特徴とする光学活性オクタヒドロビスイソキノリンにある。 A sixth aspect of the present invention is an optically active octahydrobisisoquinoline that functions as a catalyst for asymmetric coupling and is composed of (+)-octahydrobisisoquinoline.
本発明の第7の態様は、不斉カップリングの触媒として機能し、(−)−オクタヒドロビスイソキノリンからなることを特徴とする光学活性オクタヒドロビスイソキノリンにある。 A seventh aspect of the present invention is an optically active octahydrobisisoquinoline that functions as a catalyst for asymmetric coupling and is composed of (−)-octahydrobisisoquinoline.
本発明によると、ジヒドロイソキノリンを二量化してラセミ体オクタヒドロビスイソキノリンを得るに際し、ニオビウム塩を反応促進剤として用いることによりラセミ体オクタヒドロビスイソキノリンを優位に合成することができ、また、その結果得られたラセミ体オクタヒドロビスイソキノリンを光学分割することにより、(+)−及び(−)−オクタヒドロビスイソキノリンの少なくとも一方を得ることができ、得られた(+)−又は(−)−オクタヒドロビスイソキノリンは、例えば、金属との錯体とすることにより、不斉カップリングの促進剤等として用いることができる。 According to the present invention, when dihydroisoquinoline is dimerized to obtain racemic octahydrobisisoquinoline, racemic octahydrobisisoquinoline can be preferentially synthesized by using niobium salt as a reaction accelerator, By optical resolution of the resulting racemic octahydrobisisoquinoline, at least one of (+)-and (-)-octahydrobisisoquinoline can be obtained, and the obtained (+)-or (-) -Octahydrobisisoquinoline can be used as a promoter for asymmetric coupling, for example, by forming a complex with a metal.
本発明のラセミ体オクタヒドロビスイソキノリン(正式名:rac−1,1′2,2′3,3′4,4′−オクタヒドロ−1,1′−ビスイソキノリン、以下「rac−OHBI」とも略記する)の製造方法は、ジヒドロイソキノリン(正式名:3,4−ジヒドロイソキノリン)を二量化してオクタヒドロビスイソキノリン(OHBI)を得るに際し、ニオビウム塩を反応促進剤として用いる。ニオビウム塩を反応促進剤として用いることにより、ラセミ体のオクタヒドロビスイソキノリンを選択的に製造することができ、例えば、ラセミ体:メソ体=6.4:1〜14:1という高い割合でラセミ体を製造することができる(下記反応式(1))。なお、ラセミ体及びメソ体が混合したオクタヒドロビスイソキノリン全体の収率も、非特許文献1等の従来の方法よりも向上する。 Racemic octahydrobisisoquinoline of the present invention (official name: rac-1,1'2,2'3,3'4,4'-octahydro-1,1'-bisisoquinoline, hereinafter also abbreviated as "rac-OHBI") In the production method of dihydroisoquinoline (official name: 3,4-dihydroisoquinoline) to obtain octahydrobisisoquinoline (OHBI), a niobium salt is used as a reaction accelerator. By using a niobium salt as a reaction accelerator, a racemic octahydrobisisoquinoline can be selectively produced. For example, a high proportion of racemic: meso = 6.4: 1 to 14: 1 The body can be produced (the following reaction formula (1)). In addition, the overall yield of octahydrobisisoquinoline in which the racemic body and the meso body are mixed is also improved as compared with the conventional method such as Non-Patent Document 1.
ニオビウム塩としては、塩化ニオビウム、臭化ニオビウム、ヨウ化ニオビウム等を挙げることができ、塩化ニオビウムが特に好ましい。また、ニオビウムの酸化数が−1〜+5の何れの化合物でもよいが、+5のものが特に好ましい。ニオビウム塩の添加量は特に限定されないが、ジヒドロイソキノリン1モルに対して、好ましくは0.5モル以上、さらに好ましくは1.0〜2.0モル用いる。 Examples of niobium salts include niobium chloride, niobium bromide, niobium iodide, and niobium chloride is particularly preferable. Further, any compound having an oxidation number of niobium of −1 to +5 may be used, but the compound having +5 is particularly preferable. The amount of niobium salt added is not particularly limited, but is preferably 0.5 mol or more, more preferably 1.0 to 2.0 mol, per 1 mol of dihydroisoquinoline.
ニオビウム塩と共に当該ニオビウムを還元する還元剤を用いてもよい。還元剤としては、亜鉛、マグネシウム、鉄、水素化アルミニウムリチウム、水素化ホウ素ナトリウムからなる群から選択される少なくとも一種を挙げることができる。特に、安価なため亜鉛が好ましい。還元剤の添加量も特に限定されないが、ジヒドロイソキノリン1モルに対して、好ましくは1.0モル以上、さらに好ましくは1.2〜2.0モル用いる。 You may use the reducing agent which reduces the said niobium with a niobium salt. Examples of the reducing agent include at least one selected from the group consisting of zinc, magnesium, iron, lithium aluminum hydride, and sodium borohydride. In particular, zinc is preferable because it is inexpensive. The addition amount of the reducing agent is not particularly limited, but is preferably 1.0 mol or more, more preferably 1.2 to 2.0 mol, with respect to 1 mol of dihydroisoquinoline.
反応溶媒としては、メタノール、エタノール、エチレングリコール、イソプロパノール、テトラヒドロフラン(THF)、1,2−ジメトキシエタン(DME)や、これらの混合溶媒等を挙げることができるが、特に、THF−DME(10:1)混合溶媒が好ましい。 Examples of the reaction solvent include methanol, ethanol, ethylene glycol, isopropanol, tetrahydrofuran (THF), 1,2-dimethoxyethane (DME), and mixed solvents thereof. Particularly, THF-DME (10: 1) A mixed solvent is preferable.
反応させる時間や温度も特に限定されないが、反応時間は3〜5時間が好ましく、反応温度は20〜30℃が好ましい。 The reaction time and temperature are not particularly limited, but the reaction time is preferably 3 to 5 hours, and the reaction temperature is preferably 20 to 30 ° C.
反応停止剤としては、水酸化ナトリウム、水酸化カリウム等を挙げることができる。 Examples of the reaction terminator include sodium hydroxide and potassium hydroxide.
このようにして得られたオクタヒドロビスイソキノリンから、公知の方法によって、ラセミ体オクタヒドロビスイソキノリンのみを単離することができる。 Only the racemic octahydrobisisoquinoline can be isolated from the octahydrobisisoquinoline thus obtained by a known method.
なお、原料のジヒドロイソキノリンは公知の方法で得ることができる。例えば、下記のような反応で、1,2,3,4−テトラヒドロイソキノリンから製造する。 The raw material dihydroisoquinoline can be obtained by a known method. For example, it is produced from 1,2,3,4-tetrahydroisoquinoline by the following reaction.
本発明の(+)−及び(−)−オクタヒドロビスイソキノリンの製造方法は、上記の製造方法により得られたラセミ体オクタヒドロビスイソキノリンを、さらに光学分割する(下記反応式(2))。 In the method for producing (+)-and (−)-octahydrobisisoquinoline of the present invention, the racemic octahydrobisisoquinoline obtained by the above production method is further optically resolved (the following reaction formula (2)).
光学分割は、例えば、旋光性の酸を用いて行うことができる。旋光性の酸としては、(d)−及び(l)−カンファースルホン酸((d)−及び−(l)−CSA)、(d)−及び(l)−マンデル酸、光学活性カルボン酸、及び光学活性ホスホン酸からなる群から選択される少なくとも一種を用いることができるが、特にカンファースルホン酸が好ましい。d体の酸を用いると(+)−オクタヒドロビスイソキノリンを、l体の酸を用いると(−)−オクタヒドロビスイソキノリンを製造することができる。この光学分割の条件は、従来から知られている方法で行えばよく、特に限定されるものではない。光学分割の一例を具体的に説明すると、ラセミ体オクタヒドロビスイソキノリンに(d)−CSAを添加すると、(+)−オクタヒドロビスイソキノリンが結晶として生成するので、この沈殿を濾過して得た固形物をアルカリで処理する。また、濾過した際の濾液から得た固形物に(l)−CSAを添加すると、(−)−オクタヒドロビスイソキノリンを得ることができる。なお、d体又はl体の旋光性の酸を逆の順序で添加してもよい。 The optical resolution can be performed using, for example, an optical rotatory acid. Examples of the optical rotatory acid include (d)-and (l) -camphorsulfonic acid ((d)-and-(l) -CSA), (d)-and (l) -mandelic acid, optically active carboxylic acid, And at least one selected from the group consisting of optically active phosphonic acids can be used, and camphorsulfonic acid is particularly preferable. When the d-form acid is used, (+)-octahydrobisisoquinoline can be produced, and when the d-form acid is used, (-)-octahydrobisisoquinoline can be produced. Conditions for this optical division may be performed by a conventionally known method and are not particularly limited. An example of the optical resolution will be specifically described. When (d) -CSA is added to racemic octahydrobisisoquinoline, (+)-octahydrobisisoquinoline is produced as crystals, and this precipitate was obtained by filtration. Treat the solid with alkali. Moreover, (-)-octahydrobisisoquinoline can be obtained by adding (l) -CSA to the solid obtained from the filtrate at the time of filtration. The d-form or l-form optical rotatory acid may be added in the reverse order.
このようにして得られた光学活性(+)−オクタヒドロビスイソキノリン及び光学活性(−)−オクタヒドロビスイソキノリンは、例えば、不斉カップリングの触媒として機能する。 The optically active (+)-octahydrobisisoquinoline and optically active (−)-octahydrobisisoquinoline thus obtained function as, for example, a catalyst for asymmetric coupling.
また、(+)−オクタヒドロビスイソキノリン又は(−)−オクタヒドロビスイソキノリンは、それぞれ金属化合物と、金属−ジアミン錯体を形成することができる。 Moreover, (+)-octahydrobisisoquinoline or (-)-octahydrobisisoquinoline can form a metal compound and a metal-diamine complex, respectively.
金属化合物は特に限定されず、銅塩、バナジウム塩等を挙げることができ、特に銅塩であることが好ましい。銅塩としては、例えば、塩化銅、臭化銅、ヨウ化銅や、トリフルオロメタンスルホン酸銅等を挙げることができる。また、これらの金属化合物は単独でも複数種でもよい。(+)−又は(−)−オクタヒドロビスイソキノリンと金属化合物との含有割合は特に限定されないが、(+)−又は(−)−オクタヒドロビスイソキノリン1モルに対して金属化合物を好ましくは1〜2モル、さらに好ましくは1モル用いる。このような金属化合物と、(+)−オクタヒドロビスイソキノリン又は(−)−オクタヒドロビスイソキノリンとを、例えば、ジクロロメタン、アセトニトリル等の適当な溶媒中で混合することにより、金属−ジアミン錯体を合成することができる。 A metal compound is not specifically limited, A copper salt, vanadium salt, etc. can be mentioned, It is especially preferable that it is a copper salt. Examples of the copper salt include copper chloride, copper bromide, copper iodide, copper trifluoromethanesulfonate, and the like. These metal compounds may be used alone or in combination. The content ratio of (+)-or (-)-octahydrobisisoquinoline and the metal compound is not particularly limited, but the metal compound is preferably 1 with respect to 1 mole of (+)-or (-)-octahydrobisisoquinoline. ˜2 mol, more preferably 1 mol is used. A metal-diamine complex is synthesized by mixing such a metal compound with (+)-octahydrobisisoquinoline or (-)-octahydrobisisoquinoline in an appropriate solvent such as dichloromethane or acetonitrile. can do.
この金属−ジアミン錯体は、ナフトール誘導体を酸化的に不斉カップリングするナフトール誘導体の不斉カップリング方法で触媒として好適に使用することができる。このナフトール誘導体の不斉カップリング反応に使用する金属−ジアミン錯体の量は特に限定されないが、例えば、金属−ジアミン錯体中の金属量が通常のカップリング反応に使用する金属触媒と同量になる量を用いればよい。具体的には、ナフトール誘導体1モルに対して金属−ジアミン錯体を0.01モル以上用いることが好ましい。 This metal-diamine complex can be suitably used as a catalyst in an asymmetric coupling method of a naphthol derivative in which a naphthol derivative is oxidatively asymmetrically coupled. The amount of the metal-diamine complex used in the asymmetric coupling reaction of the naphthol derivative is not particularly limited. For example, the amount of metal in the metal-diamine complex is the same as the metal catalyst used in the normal coupling reaction. The amount may be used. Specifically, it is preferable to use 0.01 mol or more of metal-diamine complex with respect to 1 mol of naphthol derivative.
下記反応式(3)に示すように、(R)−OHBIと金属化合物とを触媒とした場合は、2−ナフトール誘導体を不斉カップリングして(R)−isomerを得ることができる。一方、(S)−OHBIと金属化合物とを触媒とした場合は、下記反応式(4)に示すように、2−ナフトール誘導体を不斉カップリングして(S)−isomerを得ることができる。 As shown in the following reaction formula (3), when (R) -OHBI and a metal compound are used as a catalyst, a 2-naphthol derivative can be asymmetrically coupled to obtain (R) -isomer. On the other hand, when (S) -OHBI and a metal compound are used as a catalyst, (S) -isomer can be obtained by asymmetric coupling of 2-naphthol derivatives as shown in the following reaction formula (4). .
(式中Aは、−COOR、−COR、−CONR2を表し、Rはアルキル基を表す。好ましくは、Rは炭素数1〜5のアルキル基である。) (In the formula, A represents -COOR, -COR, -CONR 2 and R represents an alkyl group. Preferably, R is an alkyl group having 1 to 5 carbon atoms.)
(式中Aは、−COOR、−COR、−CONR2を表し、Rはアルキル基を表す。好ましくは、Rは炭素数1〜5のアルキル基である。) (In the formula, A represents -COOR, -COR, -CONR 2 and R represents an alkyl group. Preferably, R is an alkyl group having 1 to 5 carbon atoms.)
不斉カップリング反応の反応溶媒としては、アセトニトリル、ジクロロメタン、メタノール、エーテル、ベンゼン、ジメチルスルホキシド(DMSO)、ジメチルホルムアミド(DMF)、テトラヒドロフラン等が挙げられる。 Examples of the reaction solvent for the asymmetric coupling reaction include acetonitrile, dichloromethane, methanol, ether, benzene, dimethyl sulfoxide (DMSO), dimethylformamide (DMF), tetrahydrofuran and the like.
反応させる時間や温度も特に限定されないが、反応時間は24時間以上が好ましく、反応温度は0〜25℃が好ましい。 The reaction time and temperature are not particularly limited, but the reaction time is preferably 24 hours or more, and the reaction temperature is preferably 0 to 25 ° C.
(実施例1)ラセミ体1,1′2,2′3,3′4,4′−オクタヒドロ−1,1′−ビスイソキノリン(rac−OHBI)の合成 Example 1 Synthesis of racemic 1,1′2,2′3,3′4,4′-octahydro-1,1′-bisisoquinoline (rac-OHBI)
500mlナスフラスコの五塩化ニオブ(6.2g,15.2mmol)に1,2−ジメトキシエタン(15ml)を加えた後、0℃にて亜鉛(1.5g,22.8mmol)を加え、30分撹拌した。その後、テトラヒドロフラン(115ml)を加えた後、3,4−ジヒドロイソキノリン(2.0g,15.2mmol)のテトラヒドロフラン(20ml)溶液を加え、室温で3時間撹拌した。0℃にて10%水酸化ナトリウム水を加え、室温で撹拌することで反応を停止させた。セライト濾過した後、酢酸エチルで抽出し、有機層を飽和食塩水で洗浄し、硫酸マグネシウムで乾燥した。溶媒留去し、ヘキサン/酢酸エチル(1/8)の混合溶媒を用い、固体を析出させ、濾取することで黄色固体(1.0g,収率50%,rac−OHBI)を得た。 1,2-Dimethoxyethane (15 ml) was added to niobium pentachloride (6.2 g, 15.2 mmol) in a 500 ml eggplant flask, and then zinc (1.5 g, 22.8 mmol) was added at 0 ° C. for 30 minutes. Stir. Thereafter, tetrahydrofuran (115 ml) was added, and a solution of 3,4-dihydroisoquinoline (2.0 g, 15.2 mmol) in tetrahydrofuran (20 ml) was added, followed by stirring at room temperature for 3 hours. The reaction was stopped by adding 10% aqueous sodium hydroxide at 0 ° C. and stirring at room temperature. After filtration through celite, extraction was performed with ethyl acetate, and the organic layer was washed with saturated brine and dried over magnesium sulfate. The solvent was distilled off, and a solid was precipitated using a mixed solvent of hexane / ethyl acetate (1/8) and collected by filtration to obtain a yellow solid (1.0 g, yield 50%, rac-OHBI).
(実施例2) (+)−(1S,1′S)−1,1′2,2′3,3′4,4′−オクタヒドロ−1,1′−ビスイソキノリン((+)−(1S,1′S)−OHBI)及び(−)−(1R,1′R)−1,1′2,2′3,3′4,4′−オクタヒドロ−1,1′−ビスイソキノリン((−)−(1R,1′R)−OHBI)の合成 Example 2 (+)-(1S, 1'S) -1,1'2,2'3,3'4,4'-octahydro-1,1'-bisisoquinoline ((+)-(1S , 1'S) -OHBI) and (-)-(1R, 1'R) -1,1'2,2'3,3'4,4'-octahydro-1,1'-bisisoquinoline ((- )-(1R, 1'R) -OHBI)
100mlナスフラスコに実施例1で得られたrac−OHBI(2.65g,10.0mmol)及びジクロロメタン(20ml)を加えた後、(d)−カンファースルホン酸(4.66g,20.0mmol)を加え、室温で30分撹拌した。溶媒留去後、ジイソプロピルエーテル、エタノールの混合溶媒で再結晶し濾取することで白色結晶を得た。得られた結晶に対し、上述の条件にて二回再結晶を繰り返した。得られた結晶を水、メタノール、ジエチルエーテルの混合溶媒に溶かし、0℃にて10%水酸化ナトリウムを加え、撹拌した後、酢酸エチルで抽出し、有機層を飽和食塩水で洗浄し、硫酸マグネシウムで乾燥した。溶媒留去することで白色固体(775mg,収率29%,>99%ee,(1S,1′S)−OHBI)を得た。 After adding rac-OHBI (2.65 g, 10.0 mmol) obtained in Example 1 and dichloromethane (20 ml) to a 100 ml eggplant flask, (d) -camphorsulfonic acid (4.66 g, 20.0 mmol) was added. In addition, the mixture was stirred at room temperature for 30 minutes. After distilling off the solvent, white crystals were obtained by recrystallization from a mixed solvent of diisopropyl ether and ethanol and filtration. The obtained crystal was recrystallized twice under the above conditions. The obtained crystals are dissolved in a mixed solvent of water, methanol and diethyl ether, 10% sodium hydroxide is added at 0 ° C., and the mixture is stirred and extracted with ethyl acetate. The organic layer is washed with saturated brine and sulfuric acid. Dried with magnesium. The solvent was distilled off to obtain a white solid (775 mg, yield 29%,> 99% ee, (1S, 1 ′S) -OHBI).
再結晶の母液に対し、溶媒留去し、水、メタノール、ジエチルエーテルの混合溶媒に溶かし、0℃にて10%水酸化ナトリウムを加え、撹拌した後、酢酸エチルで抽出し、有機層を飽和食塩水で洗浄し、硫酸マグネシウムで乾燥した。溶媒留去することで黄色固体(1.83g,収率69%,40%ee,(1R,1′R)−OHBI)を得た。得られた固体を50mlナスフラスコに入れ、ジクロロメタン(14ml)を加えた後、(l)−カンファースルホン酸(3.22g,13.8mmol)を加え、室温で30分撹拌した。溶媒留去後、ジイソプロピルエーテル、エタノールの混合溶媒で再結晶し、濾取することで白色結晶を得た。得られた結晶に対し、上述の条件にて二回再結晶を繰り返した。得られた結晶を水、メタノール、ジエチルエーテルの混合溶媒に溶かし、0℃にて10%水酸化ナトリウムを加え、撹拌した後、酢酸エチルで抽出し、有機層を飽和食塩水で洗浄し、硫酸マグネシウムで乾燥した。溶媒留去することで白色固体(810mg,収率31%,>99%ee,(1R,1′R)−OHBI)を得た。 Evaporate the solvent from the recrystallized mother liquor, dissolve in a mixed solvent of water, methanol, and diethyl ether. Add 10% sodium hydroxide at 0 ° C, stir, and extract with ethyl acetate to saturate the organic layer. Washed with brine and dried over magnesium sulfate. The solvent was distilled off to obtain a yellow solid (1.83 g, yield 69%, 40% ee, (1R, 1′R) -OHBI). The obtained solid was put into a 50 ml eggplant flask, dichloromethane (14 ml) was added, (l) -camphorsulfonic acid (3.22 g, 13.8 mmol) was added, and the mixture was stirred at room temperature for 30 minutes. After distilling off the solvent, the crystals were recrystallized with a mixed solvent of diisopropyl ether and ethanol and collected by filtration to obtain white crystals. The obtained crystal was recrystallized twice under the above conditions. The obtained crystals are dissolved in a mixed solvent of water, methanol and diethyl ether, 10% sodium hydroxide is added at 0 ° C., and the mixture is stirred and extracted with ethyl acetate. The organic layer is washed with saturated brine and sulfuric acid. Dried with magnesium. The solvent was distilled off to obtain a white solid (810 mg, yield 31%,> 99% ee, (1R, 1′R) -OHBI).
得られた(1S,1′S)−OHBI及び(1R,1′R)−OHBIの、1H−NMR、13C−NMR、融点、比旋光度、及び光学純度測定のためのHPLC測定条件を以下に示す。 HPLC measurement conditions for measuring 1 H-NMR, 13 C-NMR, melting point, specific optical rotation, and optical purity of the obtained (1S, 1 ′S) -OHBI and (1R, 1′R) -OHBI Is shown below.
Spectral Data
1H-NMR(CDCl3,400MHz)δ:2.60(2H,d,J=15.2Hz),2.80(2H,dt,J=3.2,11.5Hz),2.88-2.96(2H,m),3.18(2H,ddd,J=2.4,5.2,11.5Hz),4.68(2H,s),7.10(2H,d,J=7.2Hz,),7.15(2H,t,J=7.2Hz),7.21(2H,t,J=7.6Hz),7.36(2H,d,J=7.6Hz)
13C-NMR(CDCl3,100MHz)δ:30.4,42.8,60.1,125.1,126.0,126.2,129.3,136.6,137.3
mp113-114℃
(1S,1'S)[α]D 22,+254.8(c1.07,CHCl3)>99%ee
(1R,1'R)[α]D 22,-251.0(c1.02,CHCl3)>99%ee
*HPCL condition; カラム:DAICEL CHIRALCEL OD(ダイセル化学工業製), 移動相:Hexane/iPrOH=9/1, 流速: 0.5mL/min, R.t.:17.7min(1S,1'S),27.5min(1R,1'R)
Spectral Data
1 H-NMR (CDCl 3 , 400 MHz) δ: 2.60 (2H, d, J = 15.2 Hz), 2.80 (2H, dt, J = 3.2,11.5 Hz), 2.88-2.96 (2H, m), 3.18 (2H , ddd, J = 2.4,5.2,11.5Hz), 4.68 (2H, s), 7.10 (2H, d, J = 7.2Hz,), 7.15 (2H, t, J = 7.2Hz), 7.21 (2H, t , J = 7.6Hz), 7.36 (2H, d, J = 7.6Hz)
13 C-NMR (CDCl 3 , 100 MHz) δ: 30.4, 42.8, 60.1, 125.1, 126.0, 126.2, 129.3, 136.6, 137.3
mp113-114 ℃
(1S, 1'S) [α] D 22 , + 254.8 (c1.07, CHCl 3 )> 99% ee
(1R, 1'R) [α] D 22 , -251.0 (c1.02, CHCl 3 )> 99% ee
* HPCL condition; Column: DAICEL CHIRALCEL OD (manufactured by Daicel Chemical Industries), mobile phase: Hexane / iPrOH = 9/1, flow rate: 0.5mL / min, Rt: 17.7min (1S, 1'S), 27.5min (1R, 1 'R)
(応用実施例1) 金属−ジアミン錯体の合成 (Application Example 1) Synthesis of metal-diamine complex
25mlナスフラスコに実施例2で得られた(1R,1′R)−OHBI(50mg,0.19mmol)を量りとり、ジクロロメタン(2ml)を加えた後、塩化銅(I)(18.7mg,0.19mmol)を加え、室温で30分撹拌した。この溶液は青〜緑色であった。この溶液にヘキサン(10ml)を加えて固体を析出させ、濾取することにより、青色固体(53mg,収率77%,銅−((1R,1′R)−OHBI)錯体)を得た。 (1R, 1′R) -OHBI (50 mg, 0.19 mmol) obtained in Example 2 was weighed into a 25 ml eggplant flask, dichloromethane (2 ml) was added, and then copper (I) chloride (18.7 mg, 0.19 mmol) was added and stirred at room temperature for 30 minutes. This solution was blue to green. Hexane (10 ml) was added to this solution to precipitate a solid, which was collected by filtration to obtain a blue solid (53 mg, yield 77%, copper-((1R, 1′R) -OHBI) complex).
得られた青色固体の融点を測定したところ、90℃付近で青色から黄色に変わり、101〜102℃で融解した。 When the melting point of the obtained blue solid was measured, it changed from blue to yellow at around 90 ° C. and melted at 101 to 102 ° C.
(応用実施例2) 2−ナフトール類の不斉カップリング反応 (Application Example 2) Asymmetric coupling reaction of 2-naphthols
反応用試験管に応用実施例1で得られた銅−((1R,1′R)−OHBI)錯体(9.0mg,1:1の錯体として10mol%)を量りとり、アセトニトリル(2.5ml)を加え、0℃にて3−ヒドロキシ−2−ナフトエ酸メチル(50mg,0.25mmol)を加えた。酸素雰囲気下0℃にて48時間撹拌した後、1N塩酸にて反応を停止させた。酢酸エチルで抽出し、得られた有機層を飽和食塩水で洗浄し、硫酸マグネシウムで乾燥させた。溶媒留去した後、カラムクロマトフラフィー(シリカゲル、ヘキサン−酢酸エチル)により精製することで、黄色固体(31.9mg,収率63%,47%ee,(R)−isomer)を得た。 The copper-((1R, 1′R) -OHBI) complex (9.0 mg, 10 mol% as a 1: 1 complex) obtained in Application Example 1 was weighed into a reaction test tube, and acetonitrile (2.5 ml) was measured. ) And methyl 3-hydroxy-2-naphthoate (50 mg, 0.25 mmol) was added at 0 ° C. After stirring at 0 ° C. for 48 hours in an oxygen atmosphere, the reaction was stopped with 1N hydrochloric acid. Extraction with ethyl acetate was performed, and the resulting organic layer was washed with saturated brine and dried over magnesium sulfate. After the solvent was distilled off, the residue was purified by column chromatography (silica gel, hexane-ethyl acetate) to obtain a yellow solid (31.9 mg, yield 63%, 47% ee, (R) -isomer).
生成物の1H−NMR及びHPLC測定条件を以下に示す。 The 1 H-NMR and HPLC measurement conditions of the product are shown below.
Spectral Data
1H-NMR(CDCl3,400MHz,)d:4.05(6H,s),7.14-7.16(2H,m)7.32-7.35(4H,m)7.90-7.93(2H,m)8.68(2H,s),10.7(2H,s)
*HPLC conditions; カラム:DAICEL CHIRALPAC AD(ダイセル化学工業製), 移動相:Hexane/iPrOH=9/1, 流速: 1.0ml/min, R.t.:9.4min(S),15.5min(R)
Spectral Data
1 H-NMR (CDCl 3 , 400 MHz) d: 4.05 (6H, s), 7.14-7.16 (2H, m) 7.32-7.35 (4H, m) 7.90-7.93 (2H, m) 8.68 (2H, s) , 10.7 (2H, s)
* HPLC conditions; Column: DAICEL CHIRALPAC AD (manufactured by Daicel Chemical Industries), mobile phase: Hexane / iPrOH = 9/1, flow rate: 1.0 ml / min, Rt: 9.4 min (S), 15.5 min (R)
化学産業における機能性化合物の開発及び医農薬産業において新たな医農薬のシード分子の創成につながる。 This will lead to the development of functional compounds in the chemical industry and the creation of new seed molecules for medical and agrochemicals in the medical and agrochemical industry.
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