JP6643308B2 - プロスタグランジン及びプロスタグランジン類似体をもたらす2−置換−4−オキシ−シクロペント−2−エン−1−オンへのビニルホウ素化合物の金属触媒による非対称1,4−共役付加 - Google Patents
プロスタグランジン及びプロスタグランジン類似体をもたらす2−置換−4−オキシ−シクロペント−2−エン−1−オンへのビニルホウ素化合物の金属触媒による非対称1,4−共役付加 Download PDFInfo
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- JP6643308B2 JP6643308B2 JP2017500379A JP2017500379A JP6643308B2 JP 6643308 B2 JP6643308 B2 JP 6643308B2 JP 2017500379 A JP2017500379 A JP 2017500379A JP 2017500379 A JP2017500379 A JP 2017500379A JP 6643308 B2 JP6643308 B2 JP 6643308B2
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- 150000003180 prostaglandins Chemical class 0.000 title claims description 34
- RWMJRMPOKXSHHI-UHFFFAOYSA-N ethenylboron Chemical class [B]C=C RWMJRMPOKXSHHI-UHFFFAOYSA-N 0.000 title description 25
- 229940094443 oxytocics prostaglandins Drugs 0.000 title description 15
- 150000001875 compounds Chemical class 0.000 claims description 110
- 238000000034 method Methods 0.000 claims description 101
- -1 rhodium (I) compound Chemical class 0.000 claims description 79
- 239000000654 additive Substances 0.000 claims description 61
- 230000000996 additive effect Effects 0.000 claims description 53
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 42
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 42
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 32
- 125000000217 alkyl group Chemical group 0.000 claims description 27
- 239000004912 1,5-cyclooctadiene Substances 0.000 claims description 25
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 25
- VYXHVRARDIDEHS-UHFFFAOYSA-N 1,5-cyclooctadiene Chemical compound C1CC=CCCC=C1 VYXHVRARDIDEHS-UHFFFAOYSA-N 0.000 claims description 22
- 125000003118 aryl group Chemical group 0.000 claims description 20
- 229910052751 metal Inorganic materials 0.000 claims description 20
- 239000002184 metal Substances 0.000 claims description 20
- XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 claims description 18
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 18
- 239000002904 solvent Substances 0.000 claims description 17
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 17
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 15
- WSNODXPBBALQOF-VEJSHDCNSA-N tafluprost Chemical compound CC(C)OC(=O)CCC\C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1\C=C\C(F)(F)COC1=CC=CC=C1 WSNODXPBBALQOF-VEJSHDCNSA-N 0.000 claims description 12
- 229960004458 tafluprost Drugs 0.000 claims description 11
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 11
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 11
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 10
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 claims description 9
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical group [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 claims description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 9
- 229910052796 boron Inorganic materials 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 9
- 239000001257 hydrogen Substances 0.000 claims description 9
- FEJUGLKDZJDVFY-UHFFFAOYSA-N 9-borabicyclo(3.3.1)nonane Chemical compound C1CCC2CCCC1B2 FEJUGLKDZJDVFY-UHFFFAOYSA-N 0.000 claims description 8
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 8
- HUCVOHYBFXVBRW-UHFFFAOYSA-M caesium hydroxide Chemical compound [OH-].[Cs+] HUCVOHYBFXVBRW-UHFFFAOYSA-M 0.000 claims description 8
- 229960001342 dinoprost Drugs 0.000 claims description 8
- PXGPLTODNUVGFL-YNNPMVKQSA-N prostaglandin F2alpha Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)C[C@H](O)[C@@H]1C\C=C/CCCC(O)=O PXGPLTODNUVGFL-YNNPMVKQSA-N 0.000 claims description 8
- 125000004665 trialkylsilyl group Chemical group 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- 125000004104 aryloxy group Chemical group 0.000 claims description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- WGFOBBZOWHGYQH-MXHNKVEKSA-N lubiprostone Chemical compound O1[C@](C(F)(F)CCCC)(O)CC[C@@H]2[C@@H](CCCCCCC(O)=O)C(=O)C[C@H]21 WGFOBBZOWHGYQH-MXHNKVEKSA-N 0.000 claims description 7
- MKPLKVHSHYCHOC-AHTXBMBWSA-N travoprost Chemical compound CC(C)OC(=O)CCC\C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1\C=C\[C@@H](O)COC1=CC=CC(C(F)(F)F)=C1 MKPLKVHSHYCHOC-AHTXBMBWSA-N 0.000 claims description 7
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 125000004423 acyloxy group Chemical group 0.000 claims description 6
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 6
- 229960000345 lubiprostone Drugs 0.000 claims description 6
- 229910021645 metal ion Inorganic materials 0.000 claims description 6
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 6
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 6
- 125000004469 siloxy group Chemical group [SiH3]O* 0.000 claims description 6
- 229960002368 travoprost Drugs 0.000 claims description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 5
- 125000003342 alkenyl group Chemical group 0.000 claims description 5
- 125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 5
- 229960002470 bimatoprost Drugs 0.000 claims description 5
- AQOKCDNYWBIDND-FTOWTWDKSA-N bimatoprost Chemical compound CCNC(=O)CCC\C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1\C=C\[C@@H](O)CCC1=CC=CC=C1 AQOKCDNYWBIDND-FTOWTWDKSA-N 0.000 claims description 5
- 150000001993 dienes Chemical class 0.000 claims description 5
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 4
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 4
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 claims description 4
- 239000003446 ligand Substances 0.000 claims description 4
- 150000003284 rhodium compounds Chemical class 0.000 claims description 4
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical compound C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 claims description 4
- XFNJVJPLKCPIBV-UHFFFAOYSA-N trimethylenediamine Chemical compound NCCCN XFNJVJPLKCPIBV-UHFFFAOYSA-N 0.000 claims description 4
- 125000003821 2-(trimethylsilyl)ethoxymethyl group Chemical group [H]C([H])([H])[Si](C([H])([H])[H])(C([H])([H])[H])C([H])([H])C(OC([H])([H])[*])([H])[H] 0.000 claims description 3
- XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 claims description 3
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 claims description 3
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 3
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 3
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 3
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 3
- 150000007942 carboxylates Chemical group 0.000 claims description 3
- 229960002986 dinoprostone Drugs 0.000 claims description 3
- 150000002431 hydrogen Chemical class 0.000 claims description 3
- SJYNFBVQFBRSIB-UHFFFAOYSA-N norbornadiene Chemical compound C1=CC2C=CC1C2 SJYNFBVQFBRSIB-UHFFFAOYSA-N 0.000 claims description 3
- GMVPRGQOIOIIMI-DWKJAMRDSA-N prostaglandin E1 Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1CCCCCCC(O)=O GMVPRGQOIOIIMI-DWKJAMRDSA-N 0.000 claims description 3
- XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 claims description 3
- 125000005106 triarylsilyl group Chemical group 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- GMVPRGQOIOIIMI-UHFFFAOYSA-N (8R,11R,12R,13E,15S)-11,15-Dihydroxy-9-oxo-13-prostenoic acid Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CCCCCCC(O)=O GMVPRGQOIOIIMI-UHFFFAOYSA-N 0.000 claims description 2
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 229960000711 alprostadil Drugs 0.000 claims description 2
- 229960003395 carboprost Drugs 0.000 claims description 2
- DLJKPYFALUEJCK-MRVZPHNRSA-N carboprost Chemical compound CCCCC[C@](C)(O)\C=C\[C@H]1[C@H](O)C[C@H](O)[C@@H]1C\C=C\CCCC(O)=O DLJKPYFALUEJCK-MRVZPHNRSA-N 0.000 claims description 2
- 150000001869 cobalt compounds Chemical class 0.000 claims description 2
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 claims description 2
- 229940035429 isobutyl alcohol Drugs 0.000 claims description 2
- 229960001160 latanoprost Drugs 0.000 claims description 2
- GGXICVAJURFBLW-CEYXHVGTSA-N latanoprost Chemical compound CC(C)OC(=O)CCC\C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1CC[C@@H](O)CCC1=CC=CC=C1 GGXICVAJURFBLW-CEYXHVGTSA-N 0.000 claims description 2
- LZWQNOHZMQIFBX-UHFFFAOYSA-N lithium;2-methylpropan-2-olate Chemical compound [Li+].CC(C)(C)[O-] LZWQNOHZMQIFBX-UHFFFAOYSA-N 0.000 claims description 2
- 150000002816 nickel compounds Chemical class 0.000 claims description 2
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 claims description 2
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims 1
- 125000001153 fluoro group Chemical group F* 0.000 claims 1
- XXUPXHKCPIKWLR-JHUOEJJVSA-N isopropyl unoprostone Chemical group CCCCCCCC(=O)CC[C@H]1[C@H](O)C[C@H](O)[C@@H]1C\C=C/CCCC(=O)OC(C)C XXUPXHKCPIKWLR-JHUOEJJVSA-N 0.000 claims 1
- 229950008081 unoprostone isopropyl Drugs 0.000 claims 1
- 238000005481 NMR spectroscopy Methods 0.000 description 92
- 238000003786 synthesis reaction Methods 0.000 description 84
- 230000015572 biosynthetic process Effects 0.000 description 83
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 58
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 58
- 239000000203 mixture Substances 0.000 description 51
- 239000000243 solution Substances 0.000 description 48
- 238000006243 chemical reaction Methods 0.000 description 47
- 238000004440 column chromatography Methods 0.000 description 42
- 239000011541 reaction mixture Substances 0.000 description 41
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 37
- 239000012043 crude product Substances 0.000 description 35
- 238000001437 electrospray ionisation time-of-flight quadrupole detection Methods 0.000 description 32
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 30
- 235000019439 ethyl acetate Nutrition 0.000 description 29
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 27
- KDCIHNCMPUBDKT-UHFFFAOYSA-N hexane;propan-2-one Chemical compound CC(C)=O.CCCCCC KDCIHNCMPUBDKT-UHFFFAOYSA-N 0.000 description 27
- 239000000460 chlorine Substances 0.000 description 26
- 239000010410 layer Substances 0.000 description 24
- 238000005160 1H NMR spectroscopy Methods 0.000 description 21
- 238000013459 approach Methods 0.000 description 20
- 238000011084 recovery Methods 0.000 description 20
- 229920002554 vinyl polymer Polymers 0.000 description 20
- 239000003153 chemical reaction reagent Substances 0.000 description 19
- 238000007792 addition Methods 0.000 description 18
- 239000012044 organic layer Substances 0.000 description 17
- 238000007259 addition reaction Methods 0.000 description 16
- 239000007864 aqueous solution Substances 0.000 description 16
- 239000012267 brine Substances 0.000 description 16
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 16
- DZUXGQBLFALXCR-UHFFFAOYSA-N (+)-(9alpha,11alpha,13E,15S)-9,11,15-trihydroxyprost-13-en-1-oic acid Chemical class CCCCCC(O)C=CC1C(O)CC(O)C1CCCCCCC(O)=O DZUXGQBLFALXCR-UHFFFAOYSA-N 0.000 description 12
- 239000000543 intermediate Substances 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- 239000000741 silica gel Substances 0.000 description 11
- 229910002027 silica gel Inorganic materials 0.000 description 11
- YFXCNIVBAVFOBX-UHFFFAOYSA-N ethenylboronic acid Chemical compound OB(O)C=C YFXCNIVBAVFOBX-UHFFFAOYSA-N 0.000 description 10
- 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 10
- 238000010438 heat treatment Methods 0.000 description 10
- 125000005842 heteroatom Chemical group 0.000 description 10
- 229920006395 saturated elastomer Polymers 0.000 description 10
- VKIJXFIYBAYHOE-VOTSOKGWSA-N [(e)-2-phenylethenyl]boronic acid Chemical compound OB(O)\C=C\C1=CC=CC=C1 VKIJXFIYBAYHOE-VOTSOKGWSA-N 0.000 description 9
- KPSZWAJWFMFMFF-UHFFFAOYSA-N hept-5-enoic acid Chemical compound CC=CCCCC(O)=O KPSZWAJWFMFMFF-UHFFFAOYSA-N 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 239000002243 precursor Substances 0.000 description 9
- UORVGPXVDQYIDP-UHFFFAOYSA-N trihydridoboron Substances B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 9
- 239000003054 catalyst Substances 0.000 description 8
- DEQYTNZJHKPYEZ-UHFFFAOYSA-N ethyl acetate;heptane Chemical compound CCOC(C)=O.CCCCCCC DEQYTNZJHKPYEZ-UHFFFAOYSA-N 0.000 description 8
- 239000011734 sodium Substances 0.000 description 7
- LZPWAYBEOJRFAX-UHFFFAOYSA-N 4,4,5,5-tetramethyl-1,3,2$l^{2}-dioxaborolane Chemical compound CC1(C)O[B]OC1(C)C LZPWAYBEOJRFAX-UHFFFAOYSA-N 0.000 description 6
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 6
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 125000001424 substituent group Chemical group 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
- 125000000304 alkynyl group Chemical group 0.000 description 5
- 229910000085 borane Inorganic materials 0.000 description 5
- 229910052799 carbon Inorganic materials 0.000 description 5
- 125000001072 heteroaryl group Chemical group 0.000 description 5
- COCAUCFPFHUGAA-MGNBDDOMSA-N n-[3-[(1s,7s)-5-amino-4-thia-6-azabicyclo[5.1.0]oct-5-en-7-yl]-4-fluorophenyl]-5-chloropyridine-2-carboxamide Chemical compound C=1C=C(F)C([C@@]23N=C(SCC[C@@H]2C3)N)=CC=1NC(=O)C1=CC=C(Cl)C=N1 COCAUCFPFHUGAA-MGNBDDOMSA-N 0.000 description 5
- VUGRNZHKYVHZSN-UHFFFAOYSA-N oct-1-yn-3-ol Chemical compound CCCCCC(O)C#C VUGRNZHKYVHZSN-UHFFFAOYSA-N 0.000 description 5
- 229910052760 oxygen Inorganic materials 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 125000006239 protecting group Chemical group 0.000 description 5
- 229910052717 sulfur Inorganic materials 0.000 description 5
- YDIYEOMDOWUDTJ-UHFFFAOYSA-N 4-(dimethylamino)benzoic acid Chemical compound CN(C)C1=CC=C(C(O)=O)C=C1 YDIYEOMDOWUDTJ-UHFFFAOYSA-N 0.000 description 4
- 125000001960 7 membered carbocyclic group Chemical group 0.000 description 4
- 0 CC(C)OC(CCCC=CCC1=C[C@](*)CC1=O)=O Chemical compound CC(C)OC(CCCC=CCC1=C[C@](*)CC1=O)=O 0.000 description 4
- BZKFMUIJRXWWQK-UHFFFAOYSA-N Cyclopentenone Chemical compound O=C1CCC=C1 BZKFMUIJRXWWQK-UHFFFAOYSA-N 0.000 description 4
- 241000872931 Myoporum sandwicense Species 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- IVDFJHOHABJVEH-UHFFFAOYSA-N pinacol Chemical compound CC(C)(O)C(C)(C)O IVDFJHOHABJVEH-UHFFFAOYSA-N 0.000 description 4
- 150000003166 prostaglandin E2 derivatives Chemical class 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 230000035484 reaction time Effects 0.000 description 4
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
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- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
- 125000001231 benzoyloxy group Chemical group C(C1=CC=CC=C1)(=O)O* 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- ZENLOTPOEABINQ-UHFFFAOYSA-N bicyclo[2.2.1]hepta-1,3-diene rhodium Chemical compound [Rh].[Rh].C12=CC=C(CC1)C2 ZENLOTPOEABINQ-UHFFFAOYSA-N 0.000 description 1
- PPABCIZFQNHUIH-UHFFFAOYSA-N bicyclo[2.2.2]octa-2,5-diene Chemical compound C1=CC2CCC1C=C2 PPABCIZFQNHUIH-UHFFFAOYSA-N 0.000 description 1
- 239000004305 biphenyl Chemical group 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- XIXSBTKGTZXZFJ-UHFFFAOYSA-N bis(2,5-dimethylhex-4-en-3-yl)borane Chemical compound CC(C)=CC(C(C)C)BC(C=C(C)C)C(C)C XIXSBTKGTZXZFJ-UHFFFAOYSA-N 0.000 description 1
- MPQAQJSAYDDROO-VMAIWCPRSA-N bis[(1r,3r,4s,5r)-4,6,6-trimethyl-3-bicyclo[3.1.1]heptanyl]boron Chemical compound C([C@H]([C@@H]1C)[B][C@@H]2C[C@@H]3C[C@@H](C3(C)C)[C@H]2C)[C@H]2C(C)(C)[C@@H]1C2 MPQAQJSAYDDROO-VMAIWCPRSA-N 0.000 description 1
- 150000001639 boron compounds Chemical class 0.000 description 1
- 229910052794 bromium Inorganic materials 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
- 239000006227 byproduct Substances 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- ZDQWVKDDJDIVAL-UHFFFAOYSA-N catecholborane Chemical compound C1=CC=C2O[B]OC2=C1 ZDQWVKDDJDIVAL-UHFFFAOYSA-N 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 238000011097 chromatography purification Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- 229940125773 compound 10 Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 150000001879 copper Chemical class 0.000 description 1
- XZWQKJXJNKYMAP-UHFFFAOYSA-N cyclohexen-1-ylboronic acid Chemical compound OB(O)C1=CCCCC1 XZWQKJXJNKYMAP-UHFFFAOYSA-N 0.000 description 1
- CFIGLTVXXHKMLU-UHFFFAOYSA-N cyclopentyl hept-5-enoate Chemical compound CC=CCCCC(=O)OC1CCCC1 CFIGLTVXXHKMLU-UHFFFAOYSA-N 0.000 description 1
- WVJGKRMLCSNRKG-UHFFFAOYSA-N dibromoborane Chemical compound BrBBr WVJGKRMLCSNRKG-UHFFFAOYSA-N 0.000 description 1
- LHCGBIFHSCCRRG-UHFFFAOYSA-N dichloroborane Chemical compound ClBCl LHCGBIFHSCCRRG-UHFFFAOYSA-N 0.000 description 1
- XNYOSXARXANYPB-UHFFFAOYSA-N dicyclohexylborane Chemical compound C1CCCCC1BC1CCCCC1 XNYOSXARXANYPB-UHFFFAOYSA-N 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- HXJFQNUWPUICNY-UHFFFAOYSA-N disiamylborane Chemical compound CC(C)C(C)BC(C)C(C)C HXJFQNUWPUICNY-UHFFFAOYSA-N 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000001207 fluorophenyl group Chemical group 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- IZZWJPQHPPRVLP-UHFFFAOYSA-N hexane;2-methoxy-2-methylpropane Chemical compound CCCCCC.COC(C)(C)C IZZWJPQHPPRVLP-UHFFFAOYSA-N 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
- 150000002596 lactones Chemical class 0.000 description 1
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 1
- RMSROFOPTSOXCN-UHFFFAOYSA-N methyl 7-[3-(oxan-2-yloxy)-5-oxocyclopenten-1-yl]heptanoate Chemical compound C1C(=O)C(CCCCCCC(=O)OC)=CC1OC1OCCCC1 RMSROFOPTSOXCN-UHFFFAOYSA-N 0.000 description 1
- NIOJULSEJPAEJV-UHFFFAOYSA-N methyl 7-[3-[tert-butyl(dimethyl)silyl]oxy-5-oxocyclopenten-1-yl]heptanoate Chemical compound COC(=O)CCCCCCC1=CC(O[Si](C)(C)C(C)(C)C)CC1=O NIOJULSEJPAEJV-UHFFFAOYSA-N 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 125000006682 monohaloalkyl group Chemical group 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
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- ZCYXXKJEDCHMGH-UHFFFAOYSA-N nonane Chemical compound CCCC[CH]CCCC ZCYXXKJEDCHMGH-UHFFFAOYSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- BKIMMITUMNQMOS-UHFFFAOYSA-N normal nonane Natural products CCCCCCCCC BKIMMITUMNQMOS-UHFFFAOYSA-N 0.000 description 1
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
- DOJDQRFOTHOBEK-UHFFFAOYSA-N oct-1-en-3-yl acetate Natural products CCCCCC(C=C)OC(C)=O DOJDQRFOTHOBEK-UHFFFAOYSA-N 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 150000002900 organolithium compounds Chemical class 0.000 description 1
- 125000001979 organolithium group Chemical group 0.000 description 1
- 150000002902 organometallic compounds Chemical class 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- XOKSLPVRUOBDEW-UHFFFAOYSA-N pinane of uncertain configuration Natural products CC1CCC2C(C)(C)C1C2 XOKSLPVRUOBDEW-UHFFFAOYSA-N 0.000 description 1
- 125000006684 polyhaloalkyl group Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- WCONKKYQBKPMNZ-UHFFFAOYSA-N prop-1-en-2-ylboronic acid Chemical compound CC(=C)B(O)O WCONKKYQBKPMNZ-UHFFFAOYSA-N 0.000 description 1
- BNBXLSQYZVNUAL-IDCRAOCASA-N propan-2-yl (Z)-7-[(1R,2R)-5-oxo-2,3-bis(2-phenylethenyl)cyclopent-3-en-1-yl]hept-5-enoate Chemical compound O=C1C=C([C@@H]([C@H]1C\C=C/CCCC(=O)OC(C)C)C=CC1=CC=CC=C1)C=CC1=CC=CC=C1 BNBXLSQYZVNUAL-IDCRAOCASA-N 0.000 description 1
- BHEWSYJVETZRDF-NHWOENOTSA-N propan-2-yl (Z)-7-[(2R,3R)-3-[tert-butyl(dimethyl)silyl]oxy-2-[(E)-3,3-difluoro-4-phenoxybut-1-enyl]-5-oxocyclopentyl]hept-5-enoate Chemical compound C(C)(C)(C)[Si](O[C@H]1[C@@H](C(C(C1)=O)C\C=C/CCCC(=O)OC(C)C)\C=C\C(COC1=CC=CC=C1)(F)F)(C)C BHEWSYJVETZRDF-NHWOENOTSA-N 0.000 description 1
- JXOQWIHEUIHKFM-JRSMHYJCSA-N propan-2-yl (Z)-7-[(2R,3R)-3-[tert-butyl(dimethyl)silyl]oxy-2-[(E)-oct-1-enyl]-5-oxocyclopentyl]hept-5-enoate Chemical compound C(C)(C)(C)[Si](O[C@H]1[C@@H](C(C(C1)=O)C\C=C/CCCC(=O)OC(C)C)\C=C\CCCCCC)(C)C JXOQWIHEUIHKFM-JRSMHYJCSA-N 0.000 description 1
- SASRRPSKZULCSW-JGVZUODCSA-N propan-2-yl (Z)-7-[(2R,3R)-3-[tert-butyl(dimethyl)silyl]oxy-5-oxo-2-(2-phenylethenyl)cyclopentyl]hept-5-enoate Chemical compound C(C)(C)(C)[Si](O[C@H]1[C@@H](C(C(C1)=O)C\C=C/CCCC(=O)OC(C)C)C=CC1=CC=CC=C1)(C)C SASRRPSKZULCSW-JGVZUODCSA-N 0.000 description 1
- SECORWWIPDMVOT-IZTUGPKFSA-N propan-2-yl (z)-7-[(3r)-3-[tert-butyl(dimethyl)silyl]oxy-5-oxocyclopenten-1-yl]hept-5-enoate Chemical compound CC(C)OC(=O)CCC\C=C/CC1=C[C@H](O[Si](C)(C)C(C)(C)C)CC1=O SECORWWIPDMVOT-IZTUGPKFSA-N 0.000 description 1
- HFDZDSYCBJZTAQ-DXTPNHAXSA-N propan-2-yl (z)-7-[(3r)-3-hydroxy-5-oxocyclopenten-1-yl]hept-5-enoate Chemical compound CC(C)OC(=O)CCC\C=C/CC1=C[C@H](O)CC1=O HFDZDSYCBJZTAQ-DXTPNHAXSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000003165 prostaglandin E1 derivatives Chemical class 0.000 description 1
- 150000003169 prostaglandin F2α derivatives Chemical class 0.000 description 1
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 229910052703 rhodium Inorganic materials 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
- 230000035945 sensitivity Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- SUBJHSREKVAVAR-UHFFFAOYSA-N sodium;methanol;methanolate Chemical compound [Na+].OC.[O-]C SUBJHSREKVAVAR-UHFFFAOYSA-N 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 125000005504 styryl group Chemical group 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- MMKOSVMWXHDGEI-UHFFFAOYSA-N tert-butyl-dimethyl-oct-1-yn-3-yloxysilane Chemical compound CCCCCC(C#C)O[Si](C)(C)C(C)(C)C MMKOSVMWXHDGEI-UHFFFAOYSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 229940113006 travatan Drugs 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- PBIMIGNDTBRRPI-UHFFFAOYSA-N trifluoro borate Chemical compound FOB(OF)OF PBIMIGNDTBRRPI-UHFFFAOYSA-N 0.000 description 1
- 125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229960004317 unoprostone Drugs 0.000 description 1
- TVHAZVBUYQMHBC-SNHXEXRGSA-N unoprostone Chemical compound CCCCCCCC(=O)CC[C@H]1[C@H](O)C[C@H](O)[C@@H]1C\C=C/CCCC(O)=O TVHAZVBUYQMHBC-SNHXEXRGSA-N 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 229940018148 zioptan Drugs 0.000 description 1
- 150000003755 zirconium compounds Chemical class 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
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- 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
- C07F7/0834—Compounds having one or more O-Si linkage
-
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- 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
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- 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
- C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
- C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/48—Separation; Purification; Stabilisation; Use of additives
- C07C67/62—Use of additives, e.g. for stabilisation
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
- C07C69/73—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids
- C07C69/738—Esters of keto-carboxylic acids or aldehydo-carboxylic acids
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- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
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- 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
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Description
本願は、2014年7月10日に出願された米国仮特許出願第62/022,797号の優先権を主張するものであり、この出願の全体を参照により本明細書に援用する。
式中、
R1、R3、R4、及びR5が独立に、水素、アリール、ヘテロアリール、アルキル、アリールアルキル、アリールオキシアルキル、アルケニル、又はアルキニルを表すか;又は
R3及びR5が一緒になって、任意に環頂点として1又は2つのヘテロ原子を有する5〜7員炭素環式環を形成し、ここで、該ヘテロ原子はO、N、及びSから成る群から選択されるか;又は
R3及びR4が一緒になって、任意に環頂点として1又は2つのヘテロ原子を有する5〜7員炭素環式環を形成し、ここで、該ヘテロ原子はO、N、及びSから成る群から選択され、
そして、式中、
それぞれR1、R3、R4、及びR5が任意に、ハロゲン、ヒドロキシ、C1-4アルキル、C1-4ハロアルキル、C1-4アルコキシ、シリルオキシ、アリールオキシ、アシルオキシ、ヘテロ環式環、オキソ、COOH、CONH2、CONHC1-4アルキル、C(O)OCH2C6-10アリール、C(O)OC6-10アリール、及びC(O)OC1-4アルキルから成る群から選択される1〜3員により置換され;
R2が、水素又はヒドロキシル保護基を表し;
Xが、ホウ素含有基を表す。
II.定義
III.本発明の実施形態
式中、
R1、R3、R4、及びR5は独立に、水素、アリール、ヘテロアリール、アルキル、アリールアルキル、アリールオキシアルキル、アルケニル、又はアルキニルを表すか;又は
R3及びR5は一緒になって、任意に環頂点として1又は2つのヘテロ原子を有する5〜7員炭素環式環を形成し、ここで、該ヘテロ原子はO、N、及びSから成る群から選択されるか;又は
R3及びR4は一緒になって、任意に環頂点として1又は2つのヘテロ原子を有する5〜7員炭素環式環を形成し、ここで、該ヘテロ原子はO、N、及びSから成る群から選択され、
そして、式中、
それぞれR1、R3、R4、及びR5は任意に、ハロゲン、ヒドロキシ、C1-4アルキル、C1-4ハロアルキル、C1-4アルコキシ、シリルオキシ、アリールオキシ、アシルオキシ、ヘテロ環式環、オキソ、COOH、CONH2、CONHC1-4アルキル、C(O)OCH2C6-10アリール、C(O)OC6-10アリール、及びC(O)OC1-4アルキルから成る群から選択される1〜3員により置換され;
R2は、水素又はヒドロキシル保護基を表し;
Xは、ホウ素含有基を表す。
表1
表2
表3
表4
表5
ボロン酸3.1及び[RhCl(1,5−シクロオクタジエン)]2のそれぞれの分割添加の総量と回数、及び量の様々な変更が、2,3−二置換−4−オキシ−シクロペンタン−1−オン化合物10.1の異なった収率をもたらすことを示す。
表6
表7
a)式IV
b)ステップa)から生成物を変換して、IIIを得ること、
を含む。あるいは、式IIIのビニルホウ素化合物は、出発物質としてハロゲン化ビニルを使用して調製されることができ、そして、この変換の方法は当該技術分野で公知である。
実施例1−イソプロピル(Z)−7−[(2R,3R)−3−(tert−ブチル−ジメチルシラニルオキシ)−5−オキソ−2−スチリル−シクロペンチル]−ヘプト−5−エノアート(10.1)の合成
実施例2−イソプロピル(Z)−7−[(1R,2R)−5−オキソ−2,3−ジスチリル−シクロペント−3−エニル]−ヘプト−5−エノアート(6.1)の合成
実施例3−イソプロピル(Z)−7−{(2R,3R)−3−(tert−ブチル−ジメチル−シラニルオキシ)−2−[2−(4−メトキシ−フェニル)ビニル]−5−オキソ−シクロペンチル}−ヘプト−5−エノアート(10.2)の合成
実施例4−イソプロピル(Z)−7−[(2R,3R)−3−(tert−ブチル−ジメチル−シラニルオキシ)−5−オキソ−2−(2−p−トリル−ビニル)−シクロペンチル]−ヘプト−5−エノアート(10.3)の合成
実施例5−イソプロピル(Z)−7−[(2R,3R)−3−(tert−ブチル−ジメチル−シラニルオキシ)−5−オキソ−2−(2−m−トリル−ビニル)−シクロペンチル]−ヘプト−5−エノアート(10.4)の合成
実施例6−イソプロピル(Z)−7−[(2R,3R)−3−(tert−ブチル−ジメチル−シラニルオキシ)−2−(2−メチル−プロプ−1−エニル)−5−オキソ−シクロペンチル]−ヘプト−5−エノアート(10.5)の合成
実施例7−イソプロピル(Z)−7−[(2R,3R)−3−(tert−ブチル−ジメチル−シラニルオキシ)−2−(trans−オクタ−1−エニル)−5−オキソ−シクロペンチル]−ヘプト−5−エノアート(10.6)の合成
実施例8−イソプロピル(Z)−7−[(2R,3R)−3−(tert−ブチル−ジメチル−シラニルオキシ)−2−(trans−3,3−ジフルオロ−4−フェノキシ−ブト−1−エニル)−5−オキソ−シクロペンチル]−ヘプト−5−エノアート(10.7)の合成
実施例9−(Z)−イソプロピル7−((1R,2R,3R)−3−((tert−ブチルジメチルシリル)オキシ)−2−((E)−2−メチルスチリル)−5−オキソシクロペンチル)ヘプト−5−エノアート(10.11)の合成
実施例10−(Z)−イソプロピル7−((1R,2R,3R)−3−((tert−ブチルジメチルシリル)オキシ)−2−((E)−3−メトキシスチリル)−5−オキソシクロペンチル)ヘプト−5−エノアート(10.12)の合成
実施例11−(Z)−イソプロピル7−((1R,2R,3R)−3−((tert−ブチルジメチルシリル)オキシ)−2−((E)−4−フルオロスチリル)−5−オキソシクロペンチル)ヘプト−5−エノアート(10.13)の合成
実施例12−(Z)−イソプロピル7−((1R,2R,3R)−3−((tert−ブチルジメチルシリル)オキシ)−5−オキソ−2−((E)−4−(トリフルオロメチル)スチリル)シクロペンチル)ヘプト−5−エノアート(10.14)の合成
実施例13−(Z)−イソプロピル7−((1R,2S,3R)−3−((tert−ブチルジメチルシリル)オキシ)−5−オキソ−2−(プロプ−1−エン−2−イル)シクロペンチル)ヘプト−5−エノアート(10.15)の合成
実施例14−(Z)−イソプロピル7−((1R,2S,3R)−2−((E)−ブト−2−エン−2−イル)−3−((tert−ブチルジメチルシリル)オキシ)−5−オキソシクロペンチル)ヘプト−5−エノアート(10.16)の合成
実施例15−イソプロピル(Z)−7−[(2R,3R)−3−(tert−ブチル−ジメチル−シラニルオキシ)−5−オキソ−2−スチリル−シクロペンチル]−ヘプト−5−エノアート(10.1)の合成
実施例16−イソプロピル(Z)−7−[(2R,3R)−3−(tert−ブチル−ジメチル−シラニルオキシ)−5−オキソ−2−スチリル−シクロペンチル]−ヘプト−5−エノアート(10.1)の合成
実施例17−イソプロピル(Z)−7−[(2R,3R)−3−(tert−ブチル−ジメチル−シラニルオキシ)−5−オキソ−2−スチリル−シクロペンチル]−ヘプト−5−エノアート(10.1)の合成
実施例18−イソプロピル(Z)−7−[(2R,3R)−3−(tert−ブチル−ジメチル−シラニルオキシ)−5−オキソ−2−スチリル−シクロペンチル]−ヘプト−5−エノアート(10.1)の合成
実施例19−イソプロピル(Z)−7−[(2R,3R)−3−(tert−ブチル−ジメチル−シラニルオキシ)−5−オキソ−2−スチリル−シクロペンチル]−ヘプト−5−エノアート(10.1)の合成
実施例20−イソプロピル(Z)−7−[(2R,3R)−3−(tert−ブチル−ジメチル−シラニルオキシ)−5−オキソ−2−スチリル−シクロペンチル]−ヘプト−5−エノアート(10.1)の合成
実施例21−イソプロピル(Z)−7−[(2R,3R)−3−(tert−ブチル−ジメチル−シラニルオキシ)−5−オキソ−2−スチリル−シクロペンチル]−ヘプト−5−エノアート(10.1)の合成
実施例22−イソプロピル(Z)−7−[(2R,3R)−3−(tert−ブチル−ジメチル−シラニルオキシ)−5−オキソ−2−スチリル−シクロペンチル]−ヘプト−5−エノアート(10.1)の合成
実施例23−イソプロピル(Z)−7−[(2R,3R)−3−(tert−ブチル−ジメチル−シラニルオキシ)−5−オキソ−2−スチリル−シクロペンチル]−ヘプト−5−エノアート(10.1)の合成
実施例24−イソプロピル(Z)−7−[(2R,3R)−3−(tert−ブチル−ジメチル−シラニルオキシ)−5−オキソ−2−スチリル−シクロペンチル]−ヘプト−5−エノアート(10.1)の合成
実施例25−イソプロピル(Z)−7−[(2R,3R)−3−(tert−ブチル−ジメチル−シラニルオキシ)−5−オキソ−2−スチリル−シクロペンチル]−ヘプト−5−エノアート(10.1)の合成
実施例26−イソプロピル(Z)−7−[(2R,3R)−3−(tert−ブチル−ジメチル−シラニルオキシ)−5−オキソ−2−スチリル−シクロペンチル]−ヘプト−5−エノアート(10.1)の合成
実施例27−イソプロピル(Z)−7−[(2R,3R)−3−(tert−ブチル−ジメチル−シラニルオキシ)−5−オキソ−2−スチリル−シクロペンチル]−ヘプト−5−エノアート(10.1)の合成
実施例28−イソプロピル(Z)−7−[(2R,3R)−3−(tert−ブチル−ジメチル−シラニルオキシ)−5−オキソ−2−スチリル−シクロペンチル]−ヘプト−5−エノアート(10.1)の合成
実施例29−イソプロピル(Z)−7−[(2R,3R)−3−(tert−ブチル−ジメチル−シラニルオキシ)−5−オキソ−2−スチリル−シクロペンチル]−ヘプト−5−エノアート(10.1)の合成
実施例30−イソプロピル(Z)−7−[(2R,3R)−3−(tert−ブチル−ジメチル−シラニルオキシ)−5−オキソ−2−スチリル−シクロペンチル]−ヘプト−5−エノアート(10.1)の合成
実施例31−イソプロピル(Z)−7−[(2R,3R)−3−(tert−ブチル−ジメチル−シラニルオキシ)−5−オキソ−2−スチリル−シクロペンチル]−ヘプト−5−エノアート(10.1)の合成
実施例32−イソプロピル(Z)−7−[(2R,3R)−3−(tert−ブチル−ジメチル−シラニルオキシ)−5−オキソ−2−スチリル−シクロペンチル]−ヘプト−5−エノアート(10.1)の合成
実施例33−イソプロピル(Z)−7−[(2R,3R)−3−(tert−ブチル−ジメチル−シラニルオキシ)−5−オキソ−2−スチリル−シクロペンチル]−ヘプト−5−エノアート(10.1)の合成
実施例34−イソプロピル(Z)−7−[(2R,3R)−3−(tert−ブチル−ジメチル−シラニルオキシ)−5−オキソ−2−スチリル−シクロペンチル]−ヘプト−5−エノアート(10.1)の合成
実施例35−イソプロピル(Z)−7−[(2R,3R)−3−(tert−ブチル−ジメチル−シラニルオキシ)−5−オキソ−2−スチリル−シクロペンチル]−ヘプト−5−エノアート(10.1)の合成
実施例36−イソプロピル(Z)−7−[(2R,3R)−3−(tert−ブチル−ジメチル−シラニルオキシ)−5−オキソ−2−スチリル−シクロペンチル]−ヘプト−5−エノアート(10.1)の合成
実施例37−tert−ブチル−(1−エチニル−ヘキシルオキシ)−ジメチル−シラン(1.8a)の合成
実施例38−2−[3−(tert−ブチル−ジメチル−シラニルオキシ)−オクタ−1−エニル]−4,4,5,5−テトラメチル−[1,3,2]ジオキサボロラン(2.8a)の合成
実施例39−(E)−(3−((tert−ブチルジメチルシリル)オキシ)オクタ−1−エン−1−イル)ボロン酸(3.8a)の合成
実施例40-1−(4,4,5,5−テトラメチル[1,3,2]ジオキサボロラン−2−イル)−オクタ−1−エン−3−オール(2.8)の合成
実施例41−(E)−(3−ヒドロキシオクタ−1−エン−1−イル)ボロン酸(3.8)の合成
実施例42−オクタ−1−イン−3−イルアセタート(1.8b)の合成
実施例43−(E)−1−(4,4,5,5−テトラメチル−1,3,2−ジオキサボロラン−2−イル)オクタ−1−エン−3−イルアセタート(2.8b)の合成
実施例44−(I)−(3−アセトキシオクタ−1−エン−1−イル)ボロン酸(3.8b)の合成
実施例45-{[(1−ペンチルプロプ−2−イニル)オキシ]メチル}ベンゼン(1.8c)の合成
実施例46−(E)−2−[3−(ベンジルオキシ)オクタ−1−エン−1−イル]−4,4,5,5−テトラメチル−1,3,2−ジオキサボロラン(2.8c)の合成
実施例47−(E)−[3−(ベンジルオキシ)オクタ−1−エン−1−イル]ボロン酸(3.8c)の合成
実施例48−(E)−2−[3−(アリルオキシ)オクタ−1−エン−1−イル]−4,4,5,5−テトラメチル−1,3,2−ジオキサボロラン(2.8d)の合成
実施例49−(E)−[3−(アリルオキシ)オクタ−1−エン−1−イル]ボロン酸(3.8d)の合成
実施例50−2−(オクタ−1−イン−3−イルオキシ)テトラヒドロ−2H−ピラン(1.8e)の合成
実施例51−(E)−2−[3−(テトラヒドロ−2H−ピラノキシ)オクタ−1−エン−1−イル]−4,4,5,5−テトラメチル−1,3,2−ジオキサボロラン(2.8e)の合成
実施例52−(E)−[3−(テトラヒドロ−2H−ピラノキシ)オクタ−1−エン−1−イル]ボロン酸(3.8e)の合成
実施例53−(S)−tert−ブチルジメチル(オクタ−1−イン−3−イルオキシ)シラン(1.9a)の合成
実施例54−(S,E)−tert−ブチルジメチル{[1−(4,4,5,5−テトラメチル−1,3,2−ジオキサボロラン−2−イル)オクタ−1−エン−3−イル]オキシ}シラン(2.9a)の合成
実施例55−(S,E)−{3−[(tert−ブチルジメチルシリル)オキシ]オクタ−1−エン−1−イル}ボロン酸(3.9)の合成
実施例56−(Z)−イソプロピル7−((1R,2R,3R)−3−[(tert−ブチルジメチルシリル)オキシ]−2−{(E)−3−[(tert−ブチルジメチルシリル)オキシ]−5−フェニルペンテン−1−エン−1−イル}}−5−オキソシクロペンチル)ヘプト−5−エノアート(10.17)の合成
実施例57−(Z)−イソプロピル7−((1R,2R,3R)−3−((tert−ブチルジメチルシリル)オキシ)−2−((E)−3−((tert−ブチルジメチルシリル)オキシ)−4−(3−(トリフルオロメチル)フェノキシ)ブト−1−エン−1−イル)−5−オキソシクロペンチル)ヘプト−5−エノアート(10.18)の合成
実施例58−イソプロピル(Z)−7−{(1R,2R,3R)−2−[(1E,5E)−3−(ベンジルオキシ)−4,4−ジフルオロオクタ−1,5−ジエン−1−イル]−3−[(tert−ブチルジメチルシリル)オキシ]−5−オキソシクロペンチル}ヘプト−5−エノアート(10.19)の合成
実施例59−(Z)−イソプロピル7−{(1R,2R,3R,5S)−3−[(tert−ブチルジメチルシリル)オキシ]−2−((E)−3,3−ジフルオロ−4−フェノキシブト−1−エン−1−イル)−5−ヒドロキシシクロペンチル}ヘプト−5−エノアート(11.7)の合成
実施例60−((Z)−イソプロピル7−[(1R,2R,3R,5S)−2−((E)−3,3−ジフルオロ−4−フェノキシブト−1−エン−1−イル)−3,5−ジヒドロキシシクロペンチル]ヘプト−5−エノアート;12.7)の合成
実施例61−イソプロピル(Z)−7−((1R,2R,3R)−2−{(E)−3−アセトキシオクタ−1−エン−1−イル)−3−[(tert−ブチルジメチルシリル)オキシ]−5−オキソシクロペンチル}ヘプト−5−エノアート(10.8b)の合成
実施例62−イソプロピル(Z)−7−((1R,2R,3R)−3−[(tert−ブチルジメチルシリル)オキシ]−5−オキソ−2−{(E)−3−[(テトラヒドロ−2H−ピラン−2−イル)オキシ]オクタ−1−エン−1−イル}シクロペンチル)ヘプト−5−エノアート(10.8e)の合成
実施例63−イソプロピル(Z)−7−{(1R,2R,3R)−3−[(tert−ブチルジメチルシリル)オキシ]−2−((E)−3−ベンジルオキシ−1−エン−1−イル)−5−オキソシクロペンチル}ヘプト−5−エノアート(10.8c)の合成
実施例64−イソプロピル(Z)−7−{(1R,2R,3R)−3−[(tert−ブチルジメチルシリル)オキシ]−2−((E)−3−ヒドロキシオクタ−1−エン−1−イル)−5−オキソシクロペンチル}ヘプト−5−エノアート(10.8)の合成
実施例65−イソプロピル(Z)−7−((1R,2R,3R)−3−[(tert−ブチルジメチルシリル)オキシ]−2−{(S,E)−3−[(tert−ブチルジメチルシリル]オキシオクタ−1−エン−1−イル}−5−オキソシクロペンチル)ヘプト−5−エノアート(10.9a)の合成
実施例66−イソプロピル(Z)−7−((1R,2R,3R,5S)−3−[(tert−ブチルジメチルシリル)オキシ]−2−{(S,E)−3−[(tert−ブチルジメチルシリル)オキシ]オクタ−1−エン−1−イル}−5−ヒドロキシシクロペンチル)ヘプト−5−エノアート(11.9a)の合成
実施例67−(Z)−7−((1R,2R,3R,5S)−3−[(tert−ブチルジメチルシリル)オキシ]−2−{(S,E)−3−[(tert−ブチルジメチルシリル)オキシ]オクタ−1−エン−1−イル}−5−ヒドロキシシクロペンチル)ヘプト−5−エノアート(12.9a)の合成
実施例68−ジノプロスト(PGF2α;12.9)の合成
実施例69−イソプロピル(Z)−7−{(1R,2S,3R)−3−[(tert−ブチルジメチルシリル)オキシ]−2−(シクロヘキサ−1−エン−1−イル)−5−オキソシクロペンチル}ヘプト−5−エノアート(10.20)の合成
実施例70−メチル(E)−7−{3−[(tert−ブチルジメチルシリル)オキシ]−5−オキソ−2−スチリルシクロペンチル}ヘプタノアート(Iba)の合成
実施例71−メチル(E)−7−{5−オキソ−2−スチリル−3−[(テトラヒドロ−2H−ピラン−2−イル)オキシ]シクロペンチル}ヘプタノアート(Ibb)の合成
実施例72−イソプロピル(Z)−7−[(1R,2R,3R)−3−ヒドロキシ−5−オキソ−2−((E)−スチリル)シクロペンチル]ヘプト−5−エノアート(Iaa)の合成
実施例73−メチル(E)−7−[3−(アリルオキシ)−5−オキソ−2−スチリルシクロペンチル]ヘプタノアート(Ibc)の合成
Claims (21)
- プロスタグランジン又はその類似体を調製するための方法であって、
前記方法が、
(a)任意の塩基性添加剤の存在下において、金属添加剤を伴う溶媒中で、式II:
(b)前記式Iの化合物を、トラボプロスト、ビマトプロスト、ルビプロストン、ジノプロスト、ジノプロストン、タフルプロスト、カルボプロスト、アルプロスタジル、ラタノプロスト又はウノプロストンイソプロピルに変換すること、
を含み、
式中、
R 1 が、アルキル又はアルケニルであり、そのそれぞれが、COOH、CONH 2 、CONHC 1-4 アルキル、C(O)OCH 2 C 6-10 アリール、C(O)OC 6-10 アリール及びC(O)OC 1-4 アルキルから成る群から選択される1員により置換され;
R 3 及びR 4 が独立に、水素、アルキル、アリールアルキル、又はアリールオキシアルキルを表し、そのそれぞれが、ハロゲン、ヒドロキシ、C 1-4 ハロアルキル、C 1-4 アルコキシ、シリルオキシ、アリールオキシ、アシルオキシ、5〜7員ヘテロ環式環、及びオキソから成る群から選択される1〜3員により置換され;
R 5 が、水素であり;
R2が、水素又はヒドロキシル保護基を表し;そして、
Xが、ホウ素含有基を表す、方法。 - 前記R3が、アルキル、アリールアルキル又はアリールオキシアルキルであり、そのそれぞれが、C 1-4アルコキシ、シリルオキシ、アリールオキシ、アシルオキシ、テトラヒドロピラニル(THP)、トリフルオロメチル及びフルオロから成る群から選択される1〜3員により置換される、請求項1に記載の方法。
- 前記溶媒が、水、メタノール、エタノール、イソプロピルアルコール、イソブチルアルコール、1,4−ジオキサン、トルエン、テトラヒドロフラン(THF)、2−メチルテトラヒドロフラン(2−Me−THF)、ジグリム、アセトニトリル、N−メチルピロリドン、N,N−ジメチルホルムアミド(DMF)、N,N−ジメチルアセトアミド(DMAC)、エチレングリコール及びその組み合わせから成る群から選択される、請求項1に記載の方法。
- 前記溶媒がメタノールである、請求項4に記載の方法。
- 前記金属添加剤が、ロジウム化合物、コバルト化合物、ニッケル化合物及びその組み合わせから成る群から選択される、請求項1に記載の方法。
- 前記ロジウム化合物が、[RhCl(1,5−シクロオクタジエン)]2、[RhCl(C2H4)2]2、ジエンリガンド添加剤を伴った[RhCl(C2H4)2]2、[RhCl(ノルボルナジエン)]2、[RhOH(1,5−シクロオクタジエン)]2及びその組み合わせから成る群から選択されるロジウム(I)化合物である、請求項6に記載の方法。
- 前記ロジウム(I)化合物が、[RhCl(1,5−シクロオクタジエン)]2及び[RhOH(1,5−シクロオクタジエン)]2から成る群から選択される、請求項7に記載の方法。
- 前記塩基性添加剤が、KHF2、t−BuOLi、t−BuONa、t−BuOK、K3PO4、K2CO3、Cs2CO3、LiOH、NaOH、KOH、CsOH、KF、CsF、NaHCO3、KH2PO4、1,3−ジアミノプロパン、t−BuNH2、i−Pr2NH、ピペリジン、Et3N、2,6−ルチジン及びその組み合わせから成る群から選択される、請求項1に記載の方法。
- 前記塩基性添加剤が水酸化カリウムである、請求項9に記載の方法。
- 前記ヒドロキシル保護基が、テトラヒドロピラニル(THP)、メトキシメチル(MOM)、[2−(トリメチルシリル)エトキシ]メチル(SEM)、トリアルキルシリル、トリアリールシリル、ジアリールアルキルシリル、ベンジル、4−メトキシベンジル(PMB)、アルキルカルボニル、アリールカルボニル及びアリルから成る群から選択される、請求項1に記載の方法。
- 前記トリアルキルシリルがtert−ブチルジメチルシリル(TBS)である、請求項11に記載の方法。
- 前記ホウ素含有基Xが、B(OH)2、B(OR)2{式中、Rはアルキル基又はアリール基である}、BR2{式中、Rはアルキル基である}、BR2{式中、Rはビニル基である}、BR2{式中、Rはカルボキシラート基である}、BR{式中、Rは二座配位性カルボキシレート基である}、BR2{式中、Rはアリールオキシ基である}、BR{式中、Rは二座配位性アリールオキシ基である}、9−ボラビシクロ[3.3.1]ノナン(9−BBN)基、BF3M{式中、Mは金属イオンである}、BF3M{式中、Mはアンモニウム又はホスホニウムイオンである}並びにBR3M{式中、Rはビニル基であり及び式中、Mは金属イオンであるか又はアンモニウム若しくはホスホニウムイオンである}から成る群から選択される、請求項1に記載の方法。
- 前記ホウ素含有基Xが、B(OH)2及びBF3M{式中、Mは金属イオンである}から成る群から選択される、請求項13に記載の方法。
- 0〜80℃の温度にて実施される、請求項1に記載の方法。
- 前記塩基性添加剤が準化学量論量で使用される、請求項1に記載の方法。
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