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【结 构 式】

【分子编号】47610

【品名】((2R,3S,7S)-7-[[tert-butyl(dimethyl)silyl]oxy]-4-methylene-1-oxaspiro[2.5]oct-2-yl)methyl acetate

【CA登记号】

【 分 子 式 】C17H30O4Si

【 分 子 量 】326.5083

【元素组成】C 62.54% H 9.26% O 19.6% Si 8.6%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(II)

Oxidation of hydroxylated diene (I) with m-CPBA followed by acetylation provides epoxide (II), which is then converted to the corresponding hydroxy derivative (III) by means of SeO2 and PyO in dioxane followed by isomer separation. Treatment of compound (III) with t-butyldimethylsilyl chloride and imidazole in DMF yields the 5,7-bis-protected derivative (IV), which reacts in THF with tungsten hexachloride (WCl6) and BuLi in hexane/THF to furnish compound (V). Hydrolysis of acetate (V) with NaOH in MeOH provides alcohol (VI), which is then converted into the corresponding chloro derivative (VII) by treatment with N-chlorosuccinimide (NCS) and dimethylsulfide (Me2S) in CH2Cl2. Treatment of compound (VII) with potassium diphenylphosphide (PPh2K) in THF and aqueous H2O2 in CH2Cl2 gives diphenylphosphine oxide (VIII), which is condensed in THF with hexahydro indenone derivative (IX) by means of n-BuLi in hexane to afford compound (X). Finally, derivative (X) is deprotected by treatment with tetrabutyl ammonium fluoride in THF to yield the desired product.

1 Kiegiel, J.; et al.; Chemical conversion of vitamin D3 to its 1,25-dihydroxy metabolite. Tetrahedron Lett 1991, 32, 43, 6057.
2 Batcho, A.D.; Hennessy, B.M.; Uskokovic, M.R. (F. Hoffmann-La Roche AG); Vitamin D3 analogs. WO 0104089 .
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) 47609 2-((5S)-5-[[tert-butyl(dimethyl)silyl]oxy]-2-methylenecyclohexylidene)-1-ethanol C15H28O2Si 详情 详情
(II) 47610 ((2R,3S,7S)-7-[[tert-butyl(dimethyl)silyl]oxy]-4-methylene-1-oxaspiro[2.5]oct-2-yl)methyl acetate C17H30O4Si 详情 详情
(III) 47611 ((2R,3S,5S,7S)-7-[[tert-butyl(dimethyl)silyl]oxy]-5-hydroxy-4-methylene-1-oxaspiro[2.5]oct-2-yl)methyl acetate C17H30O5Si 详情 详情
(IV) 47612 ((2R,3S,5S,7S)-5,7-bis[[tert-butyl(dimethyl)silyl]oxy]-4-methylene-1-oxaspiro[2.5]oct-2-yl)methyl acetate C23H44O5Si2 详情 详情
(V) 47613 2-((3S,5R)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]-2-methylenecyclohexylidene)ethyl acetate C23H44O4Si2 详情 详情
(VI) 47614 2-((3S,5R)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]-2-methylenecyclohexylidene)-1-ethanol C21H42O3Si2 详情 详情
(VII) 47615 tert-butyl(dimethyl)silyl (1R,3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-5-[(E)-2-chloroethylidene]-4-methylenecyclohexyl ether; tert-butyl([(1R,3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-5-[(E)-2-chloroethylidene]-4-methylenecyclohexyl]oxy)dimethylsilane C21H41ClO2Si2 详情 详情
(VIII) 42574 [2-((3S,5R)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]-2-methylenecyclohexylidene)ethyl](oxo)diphenylphosphorane; 2-((3S,5R)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]-2-methylenecyclohexylidene)ethyl(diphenyl)phosphine oxide C33H51O3PSi2 详情 详情
(IX) 47616 (3aR,7aS)-1-[(1R)-1,5-dimethyl-5-[(trimethylsilyl)oxy]hexyl]-7a-methyl-3,3a,5,6,7,7a-hexahydro-4H-inden-4-one C21H38O2Si 详情 详情
(X) 47617   C41H78O4Si3 详情 详情
Extended Information