JP5094397B2 - 光学活性エステルの製造法 - Google Patents
光学活性エステルの製造法 Download PDFInfo
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- JP5094397B2 JP5094397B2 JP2007532175A JP2007532175A JP5094397B2 JP 5094397 B2 JP5094397 B2 JP 5094397B2 JP 2007532175 A JP2007532175 A JP 2007532175A JP 2007532175 A JP2007532175 A JP 2007532175A JP 5094397 B2 JP5094397 B2 JP 5094397B2
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- 238000004519 manufacturing process Methods 0.000 title claims description 26
- 150000002148 esters Chemical class 0.000 title description 3
- -1 2-hydroxybutyric acid ester Chemical class 0.000 claims description 49
- 238000006243 chemical reaction Methods 0.000 claims description 48
- 150000001875 compounds Chemical class 0.000 claims description 20
- 238000000034 method Methods 0.000 claims description 15
- 125000004432 carbon atom Chemical group C* 0.000 claims description 12
- 150000003573 thiols Chemical class 0.000 claims description 10
- 239000007868 Raney catalyst Substances 0.000 claims description 9
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 claims description 9
- 229910000564 Raney nickel Inorganic materials 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 238000006477 desulfuration reaction Methods 0.000 claims description 6
- 230000023556 desulfurization Effects 0.000 claims description 6
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 238000004517 catalytic hydrocracking Methods 0.000 claims description 3
- SEDGGCMDYFKAQN-UHFFFAOYSA-N 3-methyloxirane-2-carboxylic acid Chemical compound CC1OC1C(O)=O SEDGGCMDYFKAQN-UHFFFAOYSA-N 0.000 claims 2
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 claims 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
- HZXJVDYQRYYYOR-UHFFFAOYSA-K scandium(iii) trifluoromethanesulfonate Chemical compound [Sc+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F HZXJVDYQRYYYOR-UHFFFAOYSA-K 0.000 description 24
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 22
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- 230000003287 optical effect Effects 0.000 description 15
- 239000002904 solvent Substances 0.000 description 15
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 12
- 239000000243 solution Substances 0.000 description 11
- 230000002829 reductive effect Effects 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- JPJIEXKLJOWQQK-UHFFFAOYSA-K trifluoromethanesulfonate;yttrium(3+) Chemical compound [Y+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F JPJIEXKLJOWQQK-UHFFFAOYSA-K 0.000 description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 239000012230 colorless oil Substances 0.000 description 6
- 239000012044 organic layer Substances 0.000 description 6
- 230000035484 reaction time Effects 0.000 description 6
- 239000002841 Lewis acid Substances 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 150000007517 lewis acids Chemical class 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 239000002994 raw material Substances 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 238000002451 electron ionisation mass spectrometry Methods 0.000 description 4
- DNJIEGIFACGWOD-UHFFFAOYSA-N ethanethiol Chemical compound CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 4
- 238000006722 reduction reaction Methods 0.000 description 4
- 238000007142 ring opening reaction Methods 0.000 description 4
- 238000010898 silica gel chromatography Methods 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- VDFVNEFVBPFDSB-UHFFFAOYSA-N 1,3-dioxane Chemical compound C1COCOC1 VDFVNEFVBPFDSB-UHFFFAOYSA-N 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- JHUUPUMBZGWODW-UHFFFAOYSA-N 3,6-dihydro-1,2-dioxine Chemical compound C1OOCC=C1 JHUUPUMBZGWODW-UHFFFAOYSA-N 0.000 description 3
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 3
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 3
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 3
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000003905 agrochemical Substances 0.000 description 3
- QDWJUBJKEHXSMT-UHFFFAOYSA-N boranylidynenickel Chemical compound [Ni]#B QDWJUBJKEHXSMT-UHFFFAOYSA-N 0.000 description 3
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 3
- 150000002170 ethers Chemical class 0.000 description 3
- 238000005984 hydrogenation reaction Methods 0.000 description 3
- 229910052744 lithium Inorganic materials 0.000 description 3
- YVUZUKYBUMROPQ-UHFFFAOYSA-N mercury zinc Chemical compound [Zn].[Hg] YVUZUKYBUMROPQ-UHFFFAOYSA-N 0.000 description 3
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- 239000004593 Epoxy Substances 0.000 description 2
- FFEARJCKVFRZRR-UHFFFAOYSA-N L-Methionine Natural products CSCCC(N)C(O)=O FFEARJCKVFRZRR-UHFFFAOYSA-N 0.000 description 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
- 229930195722 L-methionine Natural products 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 150000001299 aldehydes Chemical group 0.000 description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 description 2
- 238000005831 deiodination reaction Methods 0.000 description 2
- WNAHIZMDSQCWRP-UHFFFAOYSA-N dodecane-1-thiol Chemical compound CCCCCCCCCCCCS WNAHIZMDSQCWRP-UHFFFAOYSA-N 0.000 description 2
- 238000000921 elemental analysis Methods 0.000 description 2
- 239000011982 enantioselective catalyst Substances 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 150000008282 halocarbons Chemical class 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 238000007327 hydrogenolysis reaction Methods 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- AUHZEENZYGFFBQ-UHFFFAOYSA-N mesitylene Substances CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 description 2
- 125000001827 mesitylenyl group Chemical group [H]C1=C(C(*)=C(C([H])=C1C([H])([H])[H])C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 229960004452 methionine Drugs 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- QMMRZOWCJAIUJA-UHFFFAOYSA-L nickel dichloride Chemical compound Cl[Ni]Cl QMMRZOWCJAIUJA-UHFFFAOYSA-L 0.000 description 2
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 2
- 150000002924 oxiranes Chemical class 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000012746 preparative thin layer chromatography Methods 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- RWOXMTPYKMNTAW-UHFFFAOYSA-N 2-hydroxy-3-phenylbutanethioic S-acid Chemical compound SC(=O)C(O)C(C)C1=CC=CC=C1 RWOXMTPYKMNTAW-UHFFFAOYSA-N 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- SKDHHIUENRGTHK-UHFFFAOYSA-N 4-nitrobenzoyl chloride Chemical compound [O-][N+](=O)C1=CC=C(C(Cl)=O)C=C1 SKDHHIUENRGTHK-UHFFFAOYSA-N 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 208000002249 Diabetes Complications Diseases 0.000 description 1
- 206010012655 Diabetic complications Diseases 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 229910021586 Nickel(II) chloride Inorganic materials 0.000 description 1
- 102000023984 PPAR alpha Human genes 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 150000001252 acrylic acid derivatives Chemical class 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([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
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 239000012954 diazonium Substances 0.000 description 1
- 150000001989 diazonium salts Chemical class 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- VYXHEFOZRVPJRK-UHFFFAOYSA-N ethyl 3-methyloxirane-2-carboxylate Chemical compound CCOC(=O)C1OC1C VYXHEFOZRVPJRK-UHFFFAOYSA-N 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- JRQFTRWEABOMKQ-UHFFFAOYSA-N fluoroform;trifluoromethanesulfonic acid Chemical compound FC(F)F.OS(=O)(=O)C(F)(F)F JRQFTRWEABOMKQ-UHFFFAOYSA-N 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- BLQJIBCZHWBKSL-UHFFFAOYSA-L magnesium iodide Chemical compound [Mg+2].[I-].[I-] BLQJIBCZHWBKSL-UHFFFAOYSA-L 0.000 description 1
- 229910001641 magnesium iodide Inorganic materials 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- VUZPPFZMUPKLLV-UHFFFAOYSA-N methane;hydrate Chemical compound C.O VUZPPFZMUPKLLV-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- PXHVJJICTQNCMI-UHFFFAOYSA-N nickel Substances [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 108091008725 peroxisome proliferator-activated receptors alpha Proteins 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 229910052706 scandium Inorganic materials 0.000 description 1
- SIXSYDAISGFNSX-UHFFFAOYSA-N scandium atom Chemical compound [Sc] SIXSYDAISGFNSX-UHFFFAOYSA-N 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 238000003797 solvolysis reaction Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- KUJHGNFSDAULEI-UHFFFAOYSA-K trialuminum oxygen(2-) phosphate Chemical compound [O-2].[O-2].[O-2].[Al+3].[Al+3].[Al+3].[O-]P([O-])([O-])=O KUJHGNFSDAULEI-UHFFFAOYSA-K 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
- VWQVUPCCIRVNHF-UHFFFAOYSA-N yttrium atom Chemical compound [Y] VWQVUPCCIRVNHF-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B53/00—Asymmetric syntheses
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/317—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by splitting-off hydrogen or functional groups; by hydrogenolysis of functional groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Description
1.工程−1
本工程は、光学活性2,3−エポキシ酪酸エステル(2)とR1−SH(ここで、R1は前記と同一のものを示す。)で表されるチオール類を、トリフルオロメタンスルホン酸スカンジウム又はトリフルオロメタンスルホン酸イットリビウムの存在下に反応させて光学活性3−アルキルチオ−2−ヒドロキシ酪酸エステル又は光学活性2−ヒドロキシ−3−フェニルチオ酪酸エステル(化合物(3))を製造する工程である。
光学活性2,3−エポキシ酪酸エステル(2)及び化合物(3)におけるRは、炭素数1〜6のアルキル基又は炭素数7〜8のアラルキル基を表し、アルキル基としては、メチル基、エチル基、n−プロピル基、イソプロピル基、n−ブチル基、イソブチル基、t−ブチル基等が好ましく、n−ブチル基がより好ましい。アラルキル基としてはベンジル基、フェネチル基等が好ましい。
使用する溶媒としては、反応に関与しないものであれば特に制限はなく、例えばジエチルエーテル、テトラヒドロフラン、1,4−あるいは1,3−ジオキサン、t−ブチルメチルエーテル、モノグライム、ジグライム等のエーテル類、ベンゼン、トルエン、キシレン、メシチレン、クロルベンゼン及びo−ジクロロベンゼン等の芳香族炭化水素類、n−ヘキサン、シクロヘキサン、n−オクタン及びn−デカン等の脂肪族炭化水素類、塩化メチレン、ジクロロエタン、クロロホルム及び四塩化炭素等のハロゲン化炭化水素類及び水等が挙げられる。このうち、ジエチルエーテル、テトラヒドロフラン、1,4−あるいは1,3−ジオキサン、t−ブチルメチルエーテル、モノグライム、ジグライム等のエーテル類、塩化メチレン、ジクロロエタン、クロロホルム及び四塩化炭素等のハロゲン化炭化水素類及び水が好ましく、塩化メチレン、クロロホルムが特に好ましい。また、これらの溶媒は、単独又は組み合わせて使用することもでき、溶媒の使用量は特に制限されない。
また、本反応は、上記使用可能な溶媒類からも分かるように、特に禁水条件を必要としない。
本工程は、化合物(3)を脱硫反応に付して、光学活性2−ヒドロキシ酪酸エステル(1)を製造する工程である。
ここで、式(1)におけるRは、前記と同じものを意味する。
実施例1
(S)−2−ヒドロキシ−(S)−3−フェニルチオ酪酸 n−ブチルの合成
(2S,3R)−2,3−エポキシ酪酸 n−ブチル(大阪有機化学工業株式会社製;100mg,97.3%ee)の塩化メチレン(5.0mL)溶液に、室温にてトリフルオロメタンスルホン酸スカンジウム[Sc(OTf)3](311mg)、チオフェノール(0.064mL)を順次加え、同温度にて10時間攪拌した。反応液を水(20mL)に加え、クロロホルム(20mL×3)で抽出した。有機層を合せて無水硫酸ナトリウムで乾燥後、減圧濃縮した。残渣をシリカゲルカラムクロマトグラフィー(n−ヘキサン/酢酸エチル=5/1)で精製し、無色油状物を得た(117mg、95.3%)。
(S)−2−ヒドロキシ−(S)−3−フェニルチオ酪酸 n−ブチルの合成
(2S,3R)−2,3−エポキシ酪酸 n−ブチル(50mg)の塩化メチレン(3.0mL)溶液に、室温にてトリフルオロメタンスルホン酸イットリビウム[Yb(OTf)3](196mg)、チオフェノール(0.032mL)を順次加え、同温度にて24時間攪拌した。反応液を水(20mL)に加え、クロロホルム(20mL×3)で抽出した。有機層を合せて無水硫酸ナトリウムで乾燥後、減圧濃縮した。残渣を分取薄層クロマトグラフィー(n−ヘキサン/酢酸エチル=5/1)で精製し、無色油状物を得た(69mg、81.3%)。
(S)−2−ヒドロキシ−(S)−3−エチルチオ酪酸 n−ブチルの合成
(2S,3R)−2,3−エポキシ酪酸 n−ブチル(100mg)の塩化メチレン(5.0mL)溶液に、室温にてトリフルオロメタンスルホン酸スカンジウム[Sc(OTf)3](311mg)、エタンチオール(0.047mL)を順次加え、同温度にて7時間攪拌した。反応液を水(20mL)に加え、クロロホルム(20mL×3)で抽出した。有機層を合せて無水硫酸ナトリウムで乾燥後、減圧濃縮した。残渣をシリカゲルカラムクロマトグラフィー(n−ヘキサン/酢酸エチル=5/1)で精製し、無色油状物を得た(116mg、83.4%)。
(S)−2−ヒドロキシ−(S)−3−ドデシルチオ酪酸 n−ブチルの合成
(2S,3R)−2,3−エポキシ酪酸 n−ブチル(50mg)の塩化メチレン(4.0mL)溶液に、室温にてトリフルオロメタンスルホン酸スカンジウム[Sc(OTf)3](156mg)、1−ドデカンチオール(0.076mL)を順次加え、同温度にて10時間攪拌した。反応液を水(20mL)に加え、クロロホルム(20mL×3)で抽出した。有機層を合せて無水硫酸ナトリウムで乾燥後、減圧濃縮した。残渣をシリカゲルカラムクロマトグラフィー(n−ヘキサン/酢酸エチル=5/1)で精製し、無色油状物を得た(97mg、84.9%)。
(S)−2−ヒドロキシ酪酸 n−ブチルの合成
(S)−2−ヒドロキシ−(S)−3−フェニルチオ酪酸 n−ブチル(60mg)をエタノール(2.0mL)に溶解し、室温にてセライト(240mg)、ラネーニッケル(360mg)のエタノール溶液(3.0mL)を順次加え、80℃にて10時間攪拌した。反応液をセライト濾過し、得られた濾液を水(20mL)に加え、ジエチルエーテル(20mL×3)で抽出した。有機層を合せて無水硫酸ナトリウムで乾燥後、減圧濃縮した。残渣をシリカゲルカラムクロマトグラフィー(塩化メチレン)で精製し、無色油状物を得た(36mg、100%)。
EI−MS m/z;161(M++H).
C8H16O3 に対する元素分析の理論値:C,59.97;H,10.07.実測値:C,60.03;H,10.09.
光学純度は下記反応式に示すように、4−ニトロ安息香酸エステルに誘導後、HPLC法で測定した。
カラム:CHIRALPAK AD
カラム温度:35℃
溶媒:n−へキサン/エタノール=60/40
流速:1mL/min.
保持時間:5.96min.(R体;4.43min.)
以下に示す化合物(2a)について、チオールとしてエタンチオール、ドデカンチオール及びチオフェノールを用い、種々のルイス酸の存在下に、化合物(3a)を製造した場合(工程−1)の結果をそれぞれ表1及び表2に示す。
Claims (3)
- 下記式(2):
で表される光学活性2,3−エポキシ酪酸エステルにトリフルオロメタンスルホン酸スカンジウムの存在下、R1−SH(ここで、R1は炭素数1〜12のアルキル基又はフェニル基を示す)で表されるチオール類を反応させて下記式(3):
で表される化合物とし、次いでこれを脱硫反応に付すことを特徴とする下記式(1):
で表される光学活性2−ヒドロキシ酪酸エステルの製造法。 - 脱硫反応が、ラネーニッケルを用いる水素化分解反応である請求項1記載の製造法。
- 下記式(2):
で表される光学活性2,3−エポキシ酪酸エステルにトリフルオロメタンスルホン酸スカンジウムの存在下、R1−SH(ここで、R1は炭素数1〜12のアルキル基又はフェニル基を示す)で表されるチオール類を反応させることを特徴とする下記式(3):
で表される化合物の製造法。
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