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【结 构 式】 
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【分子编号】16403 【品名】(4R)-2-(6-chloro-3-pyridinyl)-4-[[(2,2-dimethylpropanoyl)oxy]amino]-2-cyclohexen-1-one 【CA登记号】 |
【 分 子 式 】C16H19ClN2O3 【 分 子 量 】322.79124 【元素组成】C 59.54% H 5.93% Cl 10.98% N 8.68% O 14.87% |
合成路线1
该中间体在本合成路线中的序号：(XXXVI)9) The first asymmetric synthesis of (-)-epibatidine was disclosed by Trost and Cook through a Pd-catalyzed desymmetrization of cis-dibenzoyloxy-2-cyclohexene (XXXII) and a Pd-catalyzed cross-coupling reaction. Dibenzoate (XXXII) was reacted with trimethylsilylazide in the presence of a Pd catalyst with chiral phosphine ligands to give ent-(XXXIII) in excellent yield and e.e. (XXXIII) was converted to vinyl bromide (XXXIV), which was coupled with the stable organostannane (XXXV) through a Pd(0)-catalyzed reaction to give enone (XXXVI). Reduction of the double bond and carbonyl, O-mesylation of the resulting amido alcohol and finally heating of the crude amino mesylate in acetonitrile produced (-)-epibatidine.
| 【1】 Trost, B.M.; Cook, G.R.; An asymmetric synthesis of (-)-epibatidine. Tetrahedron Lett 1996, 37, 7485-8. |
| 【2】 Bai, D.; Xu, R.; Zhu, X.; Epibatidine. Drugs Fut 1997, 22, 11, 1210. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (rac-I) | 16385 | (+)-Epibatidine hydrochloride; (1R,2R,4S)-2-(6-chloro-3-pyridinyl)-7-azabicyclo[2.2.1]heptane | 140111-52-0 | C11H13ClN2 | 详情 | 详情 |
| rac-(XXXII) | 16399 | (1S,4R)-4-(benzoyloxy)-2-cyclohexen-1-yl benzoate | C20H18O4 | 详情 | 详情 | |
| (XXXIII) | 16400 | (1S,4R)-4-azido-2-cyclohexen-1-yl benzoate | C13H13N3O2 | 详情 | 详情 | |
| (XXXIV) | 16401 | (4R)-2-bromo-4-[[(2,2-dimethylpropanoyl)oxy]amino]-2-cyclohexen-1-one | C11H16BrNO3 | 详情 | 详情 | |
| (XXXV) | 16402 | 2-chloro-5-(tributylstannyl)pyridine | C17H30ClNSn | 详情 | 详情 | |
| (XXXVI) | 16403 | (4R)-2-(6-chloro-3-pyridinyl)-4-[[(2,2-dimethylpropanoyl)oxy]amino]-2-cyclohexen-1-one | C16H19ClN2O3 | 详情 | 详情 |