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【结 构 式】 
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【分子编号】44262 【品名】(1R,3aR,4S,7aR)-7a-methyl-1-[1-[5,5,5-trifluoro-4-hydroxy-4-(trifluoromethyl)-2-pentynyl]cyclopropyl]octahydro-1H-inden-4-ol 【CA登记号】 |
【 分 子 式 】C19H24F6O2 【 分 子 量 】398.3887792 【元素组成】C 57.28% H 6.07% F 28.61% O 8.03% |
合成路线1
该中间体在本合成路线中的序号：(VIII)The dimethylaluminium chloride-catalyzed addition of formaldehyde to the isopropenyl derivative (I) produced the homoallylic alcohol (II). The cyclopropane ring was then constructed over (II) by the Simmons-Smith procedure using diiodomethane and diethylzinc. The resulting cyclopropylethyl alcohol (III) was oxidized to aldehyde (IV) with pyridinium chlorochromate in CH2Cl2, and subsequent addition of diethyl azomethylphosphonate generated the terminal acetylene (V). The lithium acetylide of (V) was then added to hexafluoroacetone (VI), producing the propargylic alcohol (VII). Cleavage of the silyl protecting group with fluorosilicic acid liberated the secondary alcohol (VIII), which was further oxidized to ketone (IX) employing pyridinium dichromate. Condensation of this ketone (IX) with the ylide resulting from phosphine oxide (X) and n-butyllithium at low temperature produced the silylated cholecalciferol analogue (XI). Finally, desilylation with tetrabutylammonium fluoride gave the title compound.
| 【1】 Uskokovic, M.R.; Manchand, P.S. (F. Hoffmann-La Roche AG); 1,3-Dihydroxy-20,20-dialkyl-vitamin D3 analogs. EP 1015423; WO 9912894 . |
| 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) | 44255 | (1R,3aR,4S,7aR)-1-isopropenyl-7a-methyloctahydro-1H-inden-4-yl tert-butyl(dimethyl)silyl ether; [[(1R,3aR,4S,7aR)-1-isopropenyl-7a-methyloctahydro-1H-inden-4-yl]oxy](tert-butyl)dimethylsilane | C19H36OSi | 详情 | 详情 | |
| (II) | 44256 | 3-((1R,3aR,4S,7aR)-4-[[tert-butyl(dimethyl)silyl]oxy]-7a-methyloctahydro-1H-inden-1-yl)-3-buten-1-ol | C20H38O2Si | 详情 | 详情 | |
| (III) | 44257 | 2-[1-((1R,3aR,4S,7aR)-4-[[tert-butyl(dimethyl)silyl]oxy]-7a-methyloctahydro-1H-inden-1-yl)cyclopropyl]-1-ethanol | C21H40O2Si | 详情 | 详情 | |
| (IV) | 44258 | 2-[1-((1R,3aR,4S,7aR)-4-[[tert-butyl(dimethyl)silyl]oxy]-7a-methyloctahydro-1H-inden-1-yl)cyclopropyl]acetaldehyde | C21H38O2Si | 详情 | 详情 | |
| (V) | 44259 | ([(1R,3aR,4S,7aR)-7a-methyl-1-[1-(2-propynyl)cyclopropyl]octahydro-1H-inden-4-yl]oxy)(tert-butyl)dimethylsilane; (1R,3aR,4S,7aR)-7a-methyl-1-[1-(2-propynyl)cyclopropyl]octahydro-1H-inden-4-yl tert-butyl(dimethyl)silyl ether | C22H38OSi | 详情 | 详情 | |
| (VI) | 44260 | 1,1,1,3,3,3-hexafluoroacetone | 684-16-2 | C3F6O | 详情 | 详情 |
| (VII) | 44261 | 5-[1-((1R,3aR,4S,7aR)-4-[[tert-butyl(dimethyl)silyl]oxy]-7a-methyloctahydro-1H-inden-1-yl)cyclopropyl]-1,1,1-trifluoro-2-(trifluoromethyl)-3-pentyn-2-ol | C25H38F6O2Si | 详情 | 详情 | |
| (VIII) | 44262 | (1R,3aR,4S,7aR)-7a-methyl-1-[1-[5,5,5-trifluoro-4-hydroxy-4-(trifluoromethyl)-2-pentynyl]cyclopropyl]octahydro-1H-inden-4-ol | C19H24F6O2 | 详情 | 详情 | |
| (IX) | 44263 | (1R,3aR,7aR)-7a-methyl-1-[1-[5,5,5-trifluoro-4-hydroxy-4-(trifluoromethyl)-2-pentynyl]cyclopropyl]octahydro-4H-inden-4-one | C19H22F6O2 | 详情 | 详情 | |
| (X) | 30302 | [2-((3R,5R)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]cyclohexylidene)ethyl](oxo)diphenylphosphorane; 2-((3R,5R)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]cyclohexylidene)ethyl(diphenyl)phosphine oxide | C32H51O3PSi2 | 详情 | 详情 | |
| (XI) | 44264 | 5-(1-[(1R,3aS,7aR)-4-[(E)-2-((3R,5R)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]cyclohexylidene)ethylidene]-7a-methyloctahydro-1H-inden-1-yl]cyclopropyl)-1,1,1-trifluoro-2-(trifluoromethyl)-3-pentyn-2-ol | C39H62F6O3Si2 | 详情 | 详情 |