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【结 构 式】 
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【分子编号】16435 【品名】tert-butyl (1R,4S)-2-oxo-7-azabicyclo[2.2.1]heptane-7-carboxylate 【CA登记号】 |
【 分 子 式 】C11H17NO3 【 分 子 量 】211.26092 【元素组成】C 62.54% H 8.11% N 6.63% O 22.72% |
合成路线1
该中间体在本合成路线中的序号：rac-(VIII)16) A similar approach was described by Zhang and Trudell in a recent report: The known 7-azabicyclo[2.2.1]heptan-2-one (VIII) was conveniently synthesized by the [4+2] cycloaddition of methyl 3-bromopropynoate (LXVII) and N-BOC-pyrrole (LXVI). They modified Fletcher's synthesis rendering it more stereoselective and suitable for the preparation of (I) on a large scale. The tertiary alcohol (IX) was successfully deoxygenated by a radical reaction via its methyl oxalyl ester with Bu3SnH in the presence of AIBN. This afforded the deoxygenated product stereoselectively as the endo-isomer (Xa).
| 【1】 Bai, D.; Xu, R.; Zhu, X.; Epibatidine. Drugs Fut 1997, 22, 11, 1210. |
| 【2】 Zhang, C.; Trudell, M.L..; A short and efficient total synthesis of (±)-epibatidine. J Org Chem 1996, 61, 20, 7189-91. |
| 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-(LXVIII) | 16434 | 7-(tert-butyl) 2-methyl (1S,4R)-3-bromo-7-azabicyclo[2.2.1]hepta-2,5-diene-2,7-dicarboxylate | C13H16BrNO4 | 详情 | 详情 | |
| rac-(VIII) | 16435 | tert-butyl (1R,4S)-2-oxo-7-azabicyclo[2.2.1]heptane-7-carboxylate | C11H17NO3 | 详情 | 详情 | |
| rac-(IX) | 16436 | tert-butyl (1R,2S,4S)-2-(6-chloro-3-pyridinyl)-2-hydroxy-7-azabicyclo[2.2.1]heptane-7-carboxylate | C16H21ClN2O3 | 详情 | 详情 | |
| rac-(Xa) | 16437 | tert-butyl (1R,2S,4S)-2-(6-chloro-3-pyridinyl)-7-azabicyclo[2.2.1]heptane-7-carboxylate | C16H21ClN2O2 | 详情 | 详情 | |
| rac-(Xb) | 16438 | tert-butyl (1R,2R,4S)-2-(6-chloro-3-pyridinyl)-7-azabicyclo[2.2.1]heptane-7-carboxylate | C16H21ClN2O2 | 详情 | 详情 | |
| (LXVI) | 16432 | tert-Butyl pyrrole-1-carboxylate; tert-Butyl-1H-pyrrole-1-carboxylate; tert-Butyl-1-pyrrolecarboxylate | 5176-27-2 | C9H13NO2 | 详情 | 详情 |
| (LXVII) | 16433 | methyl 3-bromo-2-propynoate | C4H3BrO2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：((-)-VIII)19) Intramolecular cyclization of substituted proline derivatives. Rapoport et al. developed an asymmetric methodology which had potential for the enantiospecific synthesis of (+)- and (-)-epibatidine. The triflate (LXXIX) was readily synthesized from levulinic acid in 3 straightforward steps. Alkylation of S-thiolactam (LXXX) prepared from L-glutamic acid with triflate (LXXIX), followed by sulfide contraction provided the carbamate (LXXXI). (LXXXI) was then converted into keto acid (LXXXII). (LXXXII) was decarboxylated and the resulting iminium ions were subjected to intramolecular cyclization to give a mixture of trans-2,3-disubstituted-7-azabicyclo[2.2.1]heptanes (LXXXIII) and (LXXXIV). This mixture was selectively converted into (+)- and (-)-N-BOC-7-azabicyclo[2.2.1]heptane-2-ones (VIII), which are versatile intermediates for the enantiospecific synthesis of (+)- and (-)-epibatidine.
| 【1】 Bai, D.; Xu, R.; Zhu, X.; Epibatidine. Drugs Fut 1997, 22, 11, 1210. |
| 【2】 Hernández, A.; Marcos, M.; Rapoport, H.; Synthesis of (+)- and (-)-N-BOC-7-azabicyclo[2.2.1]heptan-2-ones, versatile intermediates for the enantiospecific synthesis of (+)- and (-)-epibatidine and analogues. J Org Chem 1995, 60, 2638-91. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| ((-)-VIII) | 16435 | tert-butyl (1R,4S)-2-oxo-7-azabicyclo[2.2.1]heptane-7-carboxylate | C11H17NO3 | 详情 | 详情 | |
| (LXIV) | 16454 | [(1R,2R,3R,4S)-7-benzyl-3-(2-oxoethyl)-7-azabicyclo[2.2.1]hept-2-yl]methyl formate | C17H21NO3 | 详情 | 详情 | |
| (LXXIX) | 16449 | methyl 3-(2-methyl-1,3-dioxolan-2-yl)-2-[[(trifluoromethyl)sulfonyl]oxy]propanoate | C9H13F3O7S | 详情 | 详情 | |
| (LXXX) | 16450 | 2-[(2S)-1-benzyl-5-thioxotetrahydro-1H-pyrrol-2-yl]-1,1-dimethylethyl formate | C16H21NO2S | 详情 | 详情 | |
| (LXXXI) | 16451 | methyl 2-[(5S)-1-benzyl-5-[2-(formyloxy)-2-methylpropyl]tetrahydro-2H-pyrrol-2-ylidene]-3-(2-methyl-1,3-dioxolan-2-yl)propanoate | C24H33NO6 | 详情 | 详情 | |
| (LXXXII) | 16452 | methyl (2S)-2-[(2R,5R)-1-benzyl-5-(formyloxy)tetrahydro-1H-pyrrol-2-yl]-4-oxopentanoate | C18H23NO5 | 详情 | 详情 | |
| (LXXXIII) | 16453 | [(1R,2S,3S,4S)-7-benzyl-3-(2-oxoethyl)-7-azabicyclo[2.2.1]hept-2-yl]methyl formate | C17H21NO3 | 详情 | 详情 |