1-[(1R,2S,4R,5R)-2-bromo-5-(6-chloro-3-pyridinyl)-7-azabicyclo[2.2.1]hept-7-yl]-2,2,2-trifluoro-1-ethanone -Drug Synthesis Database

【结构式】

【分子编号】16381

【品名】1-[(1R,2S,4R,5R)-2-bromo-5-(6-chloro-3-pyridinyl)-7-azabicyclo[2.2.1]hept-7-yl]-2,2,2-trifluoro-1-ethanone

【CA登记号】

【分子式】C₁₂H₁₄BrClN₂

【分子量】301.61334

【元素组成】C 47.79% H 4.68% Br 26.49% Cl 11.75% N 9.29%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：rac-(XIV)

3) Corey's group published a stereocontrolled route to both enantiomers of epibatidine through HPLC separation of N-(trifluoroacetyl)epibatidine using chiral columns. A Diels-Alder reaction between (Z)-alpha,beta-unsaturated ester (XI) and 1,3-butadiene furnished the cis-4,5-disubstituted cyclohexene (XII), which was converted to the vicinal dibromide (XIII). Upon treatment with t-BuOK, (XIII) underwent intramolecular nucleophilic substitution to give compound (XIV) with the azabicyclo[2.2.1]heptane ring system.

参考文献中间体

合成目标

【1】 Corey, E.J.; Loh, T.E.; Achyutha-Rao, S.; Daley, D.C.; Sarshar, S.; Stereocontrolled total synthesis of (+)- and (-)-epibatidine. J Org Chem 1993, 58, 5600-2.
【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-(XII)	16379	methyl (1R,6S)-6-(6-chloro-3-pyridinyl)-3-cyclohexene-1-carboxylate		C₁₃H₁₄ClNO₂	详情	详情
rac-(XIII)	16380	N-[(1R,2R,4S,5S)-4,5-dibromo-2-(6-chloro-3-pyridinyl)cyclohexyl]-2,2,2-trifluoroacetamide		C₁₃H₁₂Br₂ClF₃N₂O	详情	详情
rac-(XIV)	16381	1-[(1R,2S,4R,5R)-2-bromo-5-(6-chloro-3-pyridinyl)-7-azabicyclo[2.2.1]hept-7-yl]-2,2,2-trifluoro-1-ethanone		C₁₂H₁₄BrClN₂	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
(XI)	16378	methyl (Z)-3-(6-chloro-3-pyridinyl)-2-propenoate		C₉H₈ClNO₂	详情	详情

Extended Information