【结 构 式】 |
【分子编号】16376 【品名】(1R,2S,4S)-2-(6-chloro-3-pyridinyl)-7-[(2,2-dimethylpropanoyl)oxy]-7-azabicyclo[2.2.1]heptane 【CA登记号】 |
【 分 子 式 】C16H21ClN2O2 【 分 子 量 】308.80772 【元素组成】C 62.23% H 6.85% Cl 11.48% N 9.07% O 10.36% |
合成路线1
该中间体在本合成路线中的序号:(Xa)2) Fletcher and his group also utilized an intramolecular displacement to construct the azabicycloheptane ring system.4-Benzylamino-1,2-epoxycyclohexane (V) was cyclized in N-methyl-pyrrolidone upon heating to yield the exo-alcohol (VI), which was further converted into ketone (VIII). Introduction of the pyridyl group, dehydration and catalytic hydrogenation resulted primarily in the endo-isomer (Xa), which could be epimerized using t-BuOK to afford the more stable exo-isomer (Xb). Fletcher et al. also succeeded in separating the enantiomers of (VII) as their Mosher ester and in establishing the absolute configuration of (I) as (1R,2R,4S).
【1】 Fletcher, S.R.; Baker, R.; Chambers, M.S.; Hobbs, S.C.; Mitchell, P.J.; The synthesis of (+)- and (-)-epibatidine. J Chem Soc Ser Chem Commun 1993, 1216-8. |
【2】 Bai, D.; Xu, R.; Zhu, X.; Epibatidine. Drugs Fut 1997, 22, 11, 1210. |
【3】 Fletcher, S.R.; Baker, R.; Chambers, M.S.; Herbert, R.H.; Hobbs, S.C.; Thomas, S.R.; Verrier, H.M.; Watt, A.P.; Ball, R.G.; Total synthesis and determination of the absolute configuration of epibatidine. J Org Chem 1994, 59, 7, 1771-8. |
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-(VI) | 16372 | (1R,2S,4S)-7-benzyl-7-azabicyclo[2.2.1]heptan-2-ol | C13H17NO | 详情 | 详情 | |
(Xa) | 16376 | (1R,2S,4S)-2-(6-chloro-3-pyridinyl)-7-[(2,2-dimethylpropanoyl)oxy]-7-azabicyclo[2.2.1]heptane | C16H21ClN2O2 | 详情 | 详情 | |
(Xb) | 16377 | (1R,2R,4S)-2-(6-chloro-3-pyridinyl)-7-[(2,2-dimethylpropanoyl)oxy]-7-azabicyclo[2.2.1]heptane | C16H21ClN2O2 | 详情 | 详情 | |
(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 |
(V) | 16371 | N-benzyl-7-oxabicyclo[4.1.0]heptan-3-amine; N-benzyl-N-(7-oxabicyclo[4.1.0]hept-3-yl)amine | C13H17NO | 详情 | 详情 | |
(VII) | 16373 | (1R,2S,4S)-7-[(2,2-dimethylpropanoyl)oxy]-7-azabicyclo[2.2.1]heptan-2-ol | C11H19NO3 | 详情 | 详情 | |
(VIII) | 16374 | (1R,4S)-7-[(2,2-dimethylpropanoyl)oxy]-7-azabicyclo[2.2.1]heptan-2-one | C11H17NO3 | 详情 | 详情 | |
(IX) | 16375 | (1R,2S,4S)-2-(6-chloro-3-pyridinyl)-7-[(2,2-dimethylpropanoyl)oxy]-7-azabicyclo[2.2.1]heptan-2-ol | C16H21ClN2O3 | 详情 | 详情 |