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【结 构 式】 
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【分子编号】21824 【品名】[[(1R,4R)-4-[(7aR)-4-[(E)-bromomethylidene]-7a-methyloctahydro-1H-inden-1-yl]-1-(1-methyl-1-nitroethyl)pentyl]oxy](tert-butyl)dimethylsilane; (1R,4R)-4-[(7aR)-4-[(E)-bromomethylidene]-7a-methyloctahydro-1H-inden-1-yl]-1-(1-methyl-1-nitroethyl)pentyl tert-butyl(dimethyl)silyl ether 【CA登记号】 |
【 分 子 式 】C25H46BrNO3Si 【 分 子 量 】516.63468 【元素组成】C 58.12% H 8.97% Br 15.47% N 2.71% O 9.29% Si 5.44% |
合成路线1
该中间体在本合成路线中的序号：(VIII)Condensation of aldehyde (I) with 2-nitropropane (II) using tert-butyldimethylsilyl chloride, tetrabutylammonium fluoride and triethylamine afforded a mixture of diastereomeric nitroaldol products (III). After separation by column chromatography, the desired isomer was protected as the tert-butyldimethylsilyl ether (IV). Deprotection of the benzoate ester of (IV) was carried out by reduction with diisobutylaluminum hydride to provide alcohol (V), which was then oxidized to the corresponding ketone (VI) with pyridinium chlorochromate. Wittig reaction of (VI) with phosphorane (VII) provided the bromomethylene compound (VIII).
| 【1】 Oshida, J.; et al.; Synthesis and biological evaluation of 1alpha,24-dihydroxy-25-nitrovitamin D3. Bioorg Med Chem Lett 1999, 9, 3, 381. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 21818 | (4S,7aR)-7a-methyl-1-[(1R)-1-methyl-4-oxobutyl]octahydro-1H-inden-4-yl benzoate | C22H30O3 | 详情 | 详情 | |
| (II) | 21819 | 2-nitropropane | 79-46-9 | C3H7NO2 | 详情 | 详情 |
| (III) | 21820 | (4S,7aR)-1-[(1R)-4-hydroxy-1,5-dimethyl-5-nitrohexyl]-7a-methyloctahydro-1H-inden-4-yl benzoate | C25H37NO5 | 详情 | 详情 | |
| (IV) | 21821 | (4S,7aR)-1-((1R,4R)-4-[[tert-butyl(dimethyl)silyl]oxy]-1,5-dimethyl-5-nitrohexyl)-7a-methyloctahydro-1H-inden-4-yl benzoate | C31H51NO5Si | 详情 | 详情 | |
| (V) | 21822 | (4S,7aR)-1-((1R,4R)-4-[[tert-butyl(dimethyl)silyl]oxy]-1,5-dimethyl-5-nitrohexyl)-7a-methyloctahydro-1H-inden-4-ol | C24H47NO4Si | 详情 | 详情 | |
| (VI) | 21823 | (7aR)-1-((1R,4R)-4-[[tert-butyl(dimethyl)silyl]oxy]-1,5-dimethyl-5-nitrohexyl)-7a-methyloctahydro-4H-inden-4-one | C24H45NO4Si | 详情 | 详情 | |
| (VIII) | 21824 | [[(1R,4R)-4-[(7aR)-4-[(E)-bromomethylidene]-7a-methyloctahydro-1H-inden-1-yl]-1-(1-methyl-1-nitroethyl)pentyl]oxy](tert-butyl)dimethylsilane; (1R,4R)-4-[(7aR)-4-[(E)-bromomethylidene]-7a-methyloctahydro-1H-inden-1-yl]-1-(1-methyl-1-nitroethyl)pentyl tert-butyl(dimethyl)silyl ether | C25H46BrNO3Si | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VIII)Further exchange of the protecting group of (VIII) from tert-butyldimethylsilyl to trimethylsilyl ether (IX) was carried out by desilylation with LiBF4 and H2SO4, followed by treatment with (trimethylsilyl)imidazole. The resulting compound (IX) was cyclized with enyne (X) using Pd2(dba)3, Et3N and PPh3 to afford triene (XI), which was finally desilylated with pyridinium tosylate.
| 【1】 Oshida, J.; et al.; Synthesis and biological evaluation of 1alpha,24-dihydroxy-25-nitrovitamin D3. Bioorg Med Chem Lett 1999, 9, 3, 381. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VIII) | 21824 | [[(1R,4R)-4-[(7aR)-4-[(E)-bromomethylidene]-7a-methyloctahydro-1H-inden-1-yl]-1-(1-methyl-1-nitroethyl)pentyl]oxy](tert-butyl)dimethylsilane; (1R,4R)-4-[(7aR)-4-[(E)-bromomethylidene]-7a-methyloctahydro-1H-inden-1-yl]-1-(1-methyl-1-nitroethyl)pentyl tert-butyl(dimethyl)silyl ether | C25H46BrNO3Si | 详情 | 详情 | |
| (IX) | 21825 | (1R,4R)-4-[(7aR)-4-[(E)-bromomethylidene]-7a-methyloctahydro-1H-inden-1-yl]-1-(1-methyl-1-nitroethyl)pentyl trimethylsilyl ether; [[(1R,4R)-4-[(7aR)-4-[(E)-bromomethylidene]-7a-methyloctahydro-1H-inden-1-yl]-1-(1-methyl-1-nitroethyl)pentyl]oxy](trimethyl)silane | C22H40BrNO3Si | 详情 | 详情 | |
| (X) | 21826 | (5R,7S)-3,3,9,9-tetraethyl-5-(2-propynyl)-7-vinyl-4,8-dioxa-3,9-disilaundecane; (1R,3S)-1-(2-propynyl)-3-[(triethylsilyl)oxy]-4-pentenyl triethylsilyl ether | C20H40O2Si2 | 详情 | 详情 | |
| (XI) | 21827 | [[(1R,4R)-4-[(7aR)-7a-methyl-4-((E)-2-[(3S,5R)-2-methylene-3,5-bis[(triethylsilyl)oxy]cyclohexylidene]ethylidene)octahydro-1H-inden-1-yl]-1-(1-methyl-1-nitroethyl)pentyl]oxy](trimethyl)silane; (1R,4R)-4-[(7aR)-7a-methyl-4-((E)-2-[(3S,5R)-2-methylene-3,5-bis[(triethylsilyl)oxy]cyclohexylidene]ethylidene)octahydro-1H-inden-1-yl]-1-(1-methyl-1-nitroethyl)pentyl trimethylsilyl ether | C42H79NO5Si3 | 详情 | 详情 |