【结 构 式】 |
【分子编号】55608 【品名】(1R)-1-(3,4-bis{[tert-butyl(dimethyl)silyl]oxy}phenyl)-2-({4-[4-(methoxymethoxy)phenyl]butyl}amino)-1-ethanol 【CA登记号】 |
【 分 子 式 】C32H55NO5Si2 【 分 子 量 】589.96344 【元素组成】C 65.15% H 9.4% N 2.37% O 13.56% Si 9.52% |
合成路线1
该中间体在本合成路线中的序号:(XXI)Protection of 3,4-dihydroxybenzaldehyde (XVI) with t-butyldimethylsilyl chloride and imidazole provided the corresponding bis-silyl ether (XVII) (2). Asymmetric nitroaldol condensation of aldehyde (XVII) with nitromethane in the presence of the chiral samarium tris(binaphthoxide) complex (XV) --prepared from (S)-6,6'-bis(trimethylsilylethynyl)-1,1'-dihydroxy-2,2'-binaphthalene (XIV) and samarium triisopropoxide in the presence of BuLi (2,3)-- gave rise to the (R)-nitro alcohol adduct (XVIII) with high optical purity. Catalytic hydrogenation of the nitro group of (XVIII) furnished the silylated norepinephrine (XIX), which was coupled with acid (XIII) in the presence of diethylphosphoryl cyanide to yield amide (XX). Reduction of amide (XX) with LiAlH4 gave amine (XXI). The silyl and methoxymethyl protecting groups were finally removed under acidic conditions to furnish the title compound.
【1】 Takaoka, E.; et al.; Catalytic asymmetric synthesis of arbutamine. Heterocycles 1997, 46, 157. |
【2】 Shibasaki, M.; Fujita, M.; Urata, Y.; Sasai, H. (Chisso Corp.); Optically active nitro alcohol derivs., optically active amino alcohol derivates, and process for preparing the same. EP 0947498; WO 9824753 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(XIII) | 55601 | 4-[4-(methoxymethoxy)phenyl]butanoic acid | C12H16O4 | 详情 | 详情 | |
(XIV) | 55603 | C30H30O2Si2 | 详情 | 详情 | ||
(XV) | 55604 | C90H84Li3O6Si6Sm | 详情 | 详情 | ||
(XVI) | 39749 | 3,4-dihydroxybenzaldehyde | 139-85-5 | C7H6O3 | 详情 | 详情 |
(XVII) | 55602 | 3,4-bis{[tert-butyl(dimethyl)silyl]oxy}benzaldehyde | C19H34O3Si2 | 详情 | 详情 | |
(XVIII) | 55605 | (1R)-1-(3,4-bis{[tert-butyl(dimethyl)silyl]oxy}phenyl)-2-nitro-1-ethanol | C20H37NO5Si2 | 详情 | 详情 | |
(XIX) | 55606 | (1R)-2-amino-1-(3,4-bis{[tert-butyl(dimethyl)silyl]oxy}phenyl)-1-ethanol | C20H39NO3Si2 | 详情 | 详情 | |
(XX) | 55607 | N-[(2R)-2-(3,4-bis{[tert-butyl(dimethyl)silyl]oxy}phenyl)-2-hydroxyethyl]-4-[4-(methoxymethoxy)phenyl]butanamide | C32H53NO6Si2 | 详情 | 详情 | |
(XXI) | 55608 | (1R)-1-(3,4-bis{[tert-butyl(dimethyl)silyl]oxy}phenyl)-2-({4-[4-(methoxymethoxy)phenyl]butyl}amino)-1-ethanol | C32H55NO5Si2 | 详情 | 详情 |