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【结 构 式】

【分子编号】50260

【品名】(1R,2S,3S,5S)-3-(4-iodophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylic acid

【CA登记号】

【 分 子 式 】C15H18INO2

【 分 子 量 】371.21793

【元素组成】C 48.53% H 4.89% I 34.19% N 3.77% O 8.62%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(V)

Conjugate addition of 4-(trimethylsilyl)phenylmagnesium bromide (II) to anhydroecgonine methyl ester (I) afforded regioselectively the 2-beta-carbomethoxy-3-beta-aryl tropane (III). Iododesilylation of (III) using ICl or iodine in the presence of AgBF4 gave the iodophenyl derivative (IV). Hydrolysis of the ester function of (IV) in aqueous dioxan yielded the corresponding acid (V). Treatment of (V) with POCl3 provided the acid chloride (VI), which was condensed with 1,3-propanediol monomesylate (VII) to yield ester (VIII). Finally, nucleophilic displacement of the mesylate group of (VIII) with tetrabutylammonium fluoride in refluxing THF afforded the title fluoropropyl ester.

1 Gu, X.-H.; et al.; Synthesis and biological evaluation of a series of novel N- or O-fluoroalkyl derivatives of tropane: Potential positron emission tomography (PET) imaging agents for the dopamine transporter. Bioorg Med Chem Lett 2001, 11, 23, 3049.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 21118 methyl (1R,5S)-8-methyl-8-azabicyclo[3.2.1]oct-2-ene-2-carboxylate C10H15NO2 详情 详情
(II) 50257 bromo[4-(trimethylsilyl)phenyl]magnesium C9H13BrMgSi 详情 详情
(III) 50258 methyl (1R,2S,3S,5S)-8-methyl-3-[4-(trimethylsilyl)phenyl]-8-azabicyclo[3.2.1]octane-2-carboxylate C19H29NO2Si 详情 详情
(IV) 50259 methyl (1R,2S,3S,5S)-3-(4-iodophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate C16H20INO2 详情 详情
(V) 50260 (1R,2S,3S,5S)-3-(4-iodophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylic acid C15H18INO2 详情 详情
(VI) 50261 (1R,2S,3S,5S)-3-(4-iodophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carbonyl chloride C15H17ClINO 详情 详情
(VII) 50262 3-hydroxypropyl methanesulfonate C4H10O4S 详情 详情
(VIII) 50263 3-[(methylsulfonyl)oxy]propyl (1R,2S,3S,5S)-3-(4-iodophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate C19H26INO5S 详情 详情

合成路线2

该中间体在本合成路线中的序号:(V)

Conjugate addition of 4-(trimethylsilyl)phenylmagnesium bromide (II) to anhydroecgonine methyl ester (I) afforded regioselectively the 2-beta-carbomethoxy-3-beta-aryl tropane (III). Iododesilylation of (III) using ICl or iodine in the presence of AgBF4 gave the iodophenyl derivative (IV). Hydrolysis of the ester function of (IV) in aqueous dioxan yielded the corresponding acid (V). Treatment of (V) with POCl3 provided the acid chloride (VI), which was finally condensed with 2-fluoroethanol (VII) to yield the title fluoroethyl ester.

1 Gu, X.-H.; et al.; Synthesis and biological evaluation of a series of novel N- or O-fluoroalkyl derivatives of tropane: Potential positron emission tomography (PET) imaging agents for the dopamine transporter. Bioorg Med Chem Lett 2001, 11, 23, 3049.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 21118 methyl (1R,5S)-8-methyl-8-azabicyclo[3.2.1]oct-2-ene-2-carboxylate C10H15NO2 详情 详情
(II) 50257 bromo[4-(trimethylsilyl)phenyl]magnesium C9H13BrMgSi 详情 详情
(III) 50258 methyl (1R,2S,3S,5S)-8-methyl-3-[4-(trimethylsilyl)phenyl]-8-azabicyclo[3.2.1]octane-2-carboxylate C19H29NO2Si 详情 详情
(IV) 50259 methyl (1R,2S,3S,5S)-3-(4-iodophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate C16H20INO2 详情 详情
(V) 50260 (1R,2S,3S,5S)-3-(4-iodophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylic acid C15H18INO2 详情 详情
(VI) 50261 (1R,2S,3S,5S)-3-(4-iodophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carbonyl chloride C15H17ClINO 详情 详情
(VII) 44106 2-fluoro-1-ethanol 371-62-0 C2H5FO 详情 详情
Extended Information