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【结 构 式】 
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【分子编号】57150 【品名】tert-butyl(dimethyl)silyl (1R,3R)-3-{[tert-butyl(dimethyl)silyl]oxy}-5-(2-chloroethylidene)cyclohexyl ether; tert-butyl{[(1R,3R)-3-{[tert-butyl(dimethyl)silyl]oxy}-5-(2-chloroethylidene)cyclohexyl]oxy}dimethylsilane 【CA登记号】 |
【 分 子 式 】C20H41ClO2Si2 【 分 子 量 】405.16804 【元素组成】C 59.29% H 10.2% Cl 8.75% O 7.9% Si 13.86% |
合成路线1
该中间体在本合成路线中的序号：(VIII)The epoxidation of the chiral cyclohexenone (I) with H2O2 and NaOH in methanol gives the epoxide (II), which is condensed with triethyl phosphonoacetate (III) by means of NaH in THF to yield the cyclohexylidene acetate (IV). The regioselective opening of the epoxide ring of (V) by means of formic acid, Pd2(dba)3 and Bu3P in chloroform affords the cyclohexanol derivative (V), which is silylated by means of Tbdms-Cl and imidazole to provide the fully silylated compound (VI). The reduction of the ester group of (VI) by means of DIBAL in toluene gives the primary alcohol (VII) (1), which is treated with NCS and Me2S in dichloromethane to yield the chloride compound (VIII). The reaction of (VIII) with lithium diphenylphosphide, followed by oxidation with H2O2 affords the phosphine oxide (IX), which is condensed with the known synthon (X) by means of BuLi in THF to provide the silylated precursor (XI). Finally, this compound is desilylated by means of TBAF in THF to afford the target 1-alpha,25-dihydroxy-19-nor-vitamin D3.
| 【1】 Hanazawa, T.; et al.; Efficient and practical synthesis of the A-ring precursor of 19-nor-1alpha,25-dihydroxyvitamin D3 and its (3C- or 2H-labeled derivative. Org Lett 2001, 3, 14, 2205. |
| 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) | 57138 | (5S)-5-{[tert-butyl(dimethyl)silyl]oxy}-2-cyclohexen-1-one | C12H22O2Si | 详情 | 详情 | |
| (II) | 57139 | (1S,4S,6S)-4-{[tert-butyl(dimethyl)silyl]oxy}-7-oxabicyclo[4.1.0]heptan-2-one | C12H22O3Si | 详情 | 详情 | |
| (III) | 10019 | Ethyl 2-(diethoxyphosphoryl)acetate; Triethyl phosphonoacetate | 867-13-0 | C8H17O5P | 详情 | 详情 |
| (IV) | 57148 | ethyl 2-((1R,4R,6S)-4-{[tert-butyl(dimethyl)silyl]oxy}-7-oxabicyclo[4.1.0]hept-2-ylidene)acetate | C16H28O4Si | 详情 | 详情 | |
| (V) | 57149 | ethyl 2-((3R,5R)-3-{[tert-butyl(dimethyl)silyl]oxy}-5-hydroxycyclohexylidene)acetate | C16H30O4Si | 详情 | 详情 | |
| (VI) | 49047 | ethyl 2-((3R,5R)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]cyclohexylidene)acetate | C22H44O4Si2 | 详情 | 详情 | |
| (VII) | 49048 | 2-((3R,5R)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]cyclohexylidene)-1-ethanol | C20H42O3Si2 | 详情 | 详情 | |
| (VIII) | 57150 | tert-butyl(dimethyl)silyl (1R,3R)-3-{[tert-butyl(dimethyl)silyl]oxy}-5-(2-chloroethylidene)cyclohexyl ether; tert-butyl{[(1R,3R)-3-{[tert-butyl(dimethyl)silyl]oxy}-5-(2-chloroethylidene)cyclohexyl]oxy}dimethylsilane | C20H41ClO2Si2 | 详情 | 详情 | |
| (IX) | 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 | |
| (X) | 47151 | ethyl 4-[[4-(benzyloxy)-2-hydroxy-3,6-dimethylbenzoyl]oxy]-2-hydroxy-3,6-dimethylbenzoate | C27H28O7 | 详情 | 详情 | |
| (XI) | 57147 | [((1R,5R)-3-[2-((1R,7aR)-1-{(1R)-1,5-dimethyl-5-[(trimethylsilyl)oxy]hexyl}-7a-methyloctahydro-4H-inden-4-ylidene)ethylidene]-5-{[tert-butyl(dimethyl)silyl]oxy}cyclohexyl)oxy](tert-butyl)dimethylsilane; (5R)-5-{(1R,7aR)-4-[(E)-2-((3R,5R)-3,5-bis{[tert-butyl(dimethyl)silyl]oxy}cyclohexylidene)ethylidene]-7a-methyloctahydro-4H-inden-1-yl}-1,1-dimethylhexyl trimethylsilyl ether | C41H80O3Si3 | 详情 | 详情 |