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【结 构 式】 
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【分子编号】58596 【品名】methyl 4-(3,4-dichlorophenyl)-1-hydroxy-4-phenylbutylcarbamate 【CA登记号】 |
【 分 子 式 】C18H19Cl2NO3 【 分 子 量 】368.2592 【元素组成】C 58.71% H 5.2% Cl 19.25% N 3.8% O 13.03% |
合成路线1
该中间体在本合成路线中的序号：(V)The reaction of intermediate 4-(3,4-dichlorophenyl)-4-phenylbutyric acid (I) (see scheme number 09017202a intermediate (VII)) with (COCl)2 in dichloromethane gives the acyl chloride (II), which is condensed with methyl carbamate (III) in hot toluene to yield N-[4-(3,4-dichlorophenyl)-4-phenylbutyryl]carbamic acid methyl ester (IV). The reduction of (IV) with DIBAL in toluene/dichloromethane affords the hydroxybutyl derivative (V), which is cyclized by means of TiCl4 in dichloromethane to provide N-[4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthyl]carbamic acid methyl ester as a mixture of the cis and trans isomers, easily separated by chromatography. Finally, the desired cis isomer (VI) is reduced with LiAlH4 in THF to afford the target (rac)-sertraline.
| 【1】 DeNinno, M.P.; et al.; The preparation and intra- and intermolecular addition reactions of acyclic N-acylimines: Applications to the synthesis of (±)-sertraline. J Org Chem 2001, 66, 21, 6988. |
| 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) | 30581 | 4-(3,4-dichlorophenyl)-4-phenylbutyric acid | C16H14Cl2O2 | 详情 | 详情 | |
| (II) | 30582 | 4-(3,4-dichlorophenyl)-4-phenylbutanoyl chloride | C16H13Cl3O | 详情 | 详情 | |
| (III) | 40724 | methyl carbamate; carbamic acid methyl ester | 598-55-0 | C2H5NO2 | 详情 | 详情 |
| (IV) | 58595 | methyl 4-(3,4-dichlorophenyl)-4-phenylbutanoylcarbamate | C18H17Cl2NO3 | 详情 | 详情 | |
| (V) | 58596 | methyl 4-(3,4-dichlorophenyl)-1-hydroxy-4-phenylbutylcarbamate | C18H19Cl2NO3 | 详情 | 详情 | |
| (VI) | 34049 | methyl (1S,4S)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthalenylcarbamate | C18H17Cl2NO2 | 详情 | 详情 |