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【结 构 式】 
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【分子编号】59871 【品名】ethyl 2-((3R,4R,5R)-3,5-bis{[tert-butyl(diphenyl)silyl]oxy}-4-hydroxy-2-methylenecyclohexylidene)acetate 【CA登记号】 |
【 分 子 式 】C43H52O5Si2 【 分 子 量 】705.05388 【元素组成】C 73.25% H 7.43% O 11.35% Si 7.97% |
合成路线1
该中间体在本合成路线中的序号：(XXIV)Hydrogenolysis of the isoxazoline ring of (XV) in the presence of Raney-nickel and boric acid generated the (hydroxymethyl)cyclohexanone (XVI). After hydroxyl group protection of (XVI) as the silyl ether (XVII), Peterson olefination of the ketone function of (XVII) with the lithium derivative of ethyl trimethylsilylacetate (XVIII) furnished the unsaturated ester (XIX). Desilylation of (XIX) gave the primary alcohol (XX), which was dehydrated to (XXI) by treatment with methanesulfonyl chloride and pyridine. The 1-(ethoxy)ethoxy protecting group of (XXI) was then replaced by a silyl ether (XXII) by acidic ketal hydrolysis, followed by treatment with tert-butyldiphenylsilyl chloride and imidazole. Subsequent acetonide (XXII) hydrolysis gave diol (XXIII), which was regioselectively mono-silylated providing intermediate (XXIV)
| 【1】 Takahashi, T.; Shiono, M. (Kuraray Co., Ltd.); Cyclohexanetriol derivs.. EP 0503630 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XV) | 59863 | (3aR,4R,8bR)-2,2-dimethyl-3a,4,5,8,8a,8b-hexahydro[1,3]dioxolo[4,5-e][2,1]benzisoxazol-4-yl 1-ethoxyethyl ether; (3aR,4R,8bR)-4-(1-ethoxyethoxy)-2,2-dimethyl-3a,4,5,8,8a,8b-hexahydro[1,3]dioxolo[4,5-e][2,1]benzisoxazole | C14H23NO5 | 详情 | 详情 | |
| (XVI) | 59864 | (3aR,7R,7aR)-7-(1-ethoxyethoxy)-4-(hydroxymethyl)-2,2-dimethyltetrahydro-1,3-benzodioxol-5(4H)-one | C14H24O6 | 详情 | 详情 | |
| (XVII) | 59865 | (3aR,7R,7aR)-4-({[tert-butyl(dimethyl)silyl]oxy}methyl)-7-(1-ethoxyethoxy)-2,2-dimethyltetrahydro-1,3-benzodioxol-5(4H)-one | C20H38O6Si | 详情 | 详情 | |
| (XVIII) | 49044 | ethyl 2-(trimethylsilyl)acetate | C7H16O2Si | 详情 | 详情 | |
| (XIX) | 59867 | ethyl 2-[(3aR,7R,7aR)-4-({[tert-butyl(dimethyl)silyl]oxy}methyl)-7-(1-ethoxyethoxy)-2,2-dimethyltetrahydro-1,3-benzodioxol-5(4H)-ylidene]acetate | C24H44O7Si | 详情 | 详情 | |
| (XX) | 59866 | ethyl 2-[(3aR,7R,7aR)-7-(1-ethoxyethoxy)-4-(hydroxymethyl)-2,2-dimethyltetrahydro-1,3-benzodioxol-5(4H)-ylidene]acetate | C18H30O7 | 详情 | 详情 | |
| (XXI) | 59868 | ethyl 2-[(3aR,7R,7aR)-7-(1-ethoxyethoxy)-2,2-dimethyl-4-methylenetetrahydro-1,3-benzodioxol-5(4H)-ylidene]acetate | C18H28O6 | 详情 | 详情 | |
| (XXII) | 59869 | ethyl 2-[(3aR,7R,7aS)-7-{[tert-butyl(diphenyl)silyl]oxy}-2,2-dimethyl-4-methylenetetrahydro-1,3-benzodioxol-5(4H)-ylidene]acetate | C30H38O5Si | 详情 | 详情 | |
| (XXIII) | 59870 | ethyl 2-((3R,4S,5R)-5-{[tert-butyl(diphenyl)silyl]oxy}-3,4-dihydroxy-2-methylenecyclohexylidene)acetate | C27H34O5Si | 详情 | 详情 | |
| (XXIV) | 59871 | ethyl 2-((3R,4R,5R)-3,5-bis{[tert-butyl(diphenyl)silyl]oxy}-4-hydroxy-2-methylenecyclohexylidene)acetate | C43H52O5Si2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XXIV)Reduction of the ester function of (XXIV) by means of DIBAL afforded alcohol (XXV), which was further protected as the tetrahydropyranyl ether (XXVI). The free secondary hydroxyl of (XXVI) was then alkylated with allyl bromide (XXVII) and NaH to produce the allyl ether (XXVIII). Selective olefin hydroboration at the allyl ether moiety of (XXVIII), followed by oxidative work-up gave rise to the primary alcohol (XXIX). After silylation of (XXIX), the tetrahydropyranyl ether was hydrolyzed with ethanolic HCl providing the tris-O-silylated compound (XXX)
| 【1】 Takahashi, T.; Shiono, M. (Kuraray Co., Ltd.); Cyclohexanetriol derivs.. EP 0503630 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXIV) | 59871 | ethyl 2-((3R,4R,5R)-3,5-bis{[tert-butyl(diphenyl)silyl]oxy}-4-hydroxy-2-methylenecyclohexylidene)acetate | C43H52O5Si2 | 详情 | 详情 | |
| (XXV) | 59872 | (1R,2R,6R)-2,6-bis{[tert-butyl(diphenyl)silyl]oxy}-4-[(Z)-2-hydroxyethylidene]-3-methylenecyclohexanol | C41H50O4Si2 | 详情 | 详情 | |
| (XXVI) | 59873 | (1R,2R,6R)-2,6-bis{[tert-butyl(diphenyl)silyl]oxy}-3-methylene-4-[(Z)-2-(tetrahydro-2H-pyran-2-yloxy)ethylidene]cyclohexanol | C46H58O5Si2 | 详情 | 详情 | |
| (XXVII) | 11463 | 3-Bromo-1-propene; 3-Bromopropene；allyl bromide | 106-95-6 | C3H5Br | 详情 | 详情 |
| (XXVIII) | 59874 | ({(1R,2R,3R)-2-(allyloxy)-3-{[tert-butyl(diphenyl)silyl]oxy}-4-methylene-5-[(Z)-2-(tetrahydro-2H-pyran-2-yloxy)ethylidene]cyclohexyl}oxy)(tert-butyl)diphenylsilane; allyl (1R,2R,6R)-2,6-bis{[tert-butyl(diphenyl)silyl]oxy}-3-methylene-4-[(Z)-2-(tetrahydro-2H-pyran-2-yloxy)ethylidene]cyclohexyl ether | C49H62O5Si2 | 详情 | 详情 | |
| (XXIX) | 59875 | 3-({(1R,2R,6R)-2,6-bis{[tert-butyl(diphenyl)silyl]oxy}-3-methylene-4-[(Z)-2-(tetrahydro-2H-pyran-2-yloxy)ethylidene]cyclohexyl}oxy)-1-propanol | C49H64O6Si2 | 详情 | 详情 | |
| (XXX) | 59876 | 2-[(3R,4R,5R)-3,5-bis{[tert-butyl(diphenyl)silyl]oxy}-4-(3-{[tert-butyl(diphenyl)silyl]oxy}propoxy)-2-methylenecyclohexylidene]-1-ethanol | C60H74O5Si3 | 详情 | 详情 |