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【结 构 式】 
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【分子编号】41974 【品名】4,4'-Difluorobenzhydrol; bis(4-Fluorophenyl)methanol; alpha-(4-fluorophenyl)benzenemethanol; 4-fluoro-alpha-(4-fluorophenyl)benzenemethanol 【CA登记号】365-24-2 |
【 分 子 式 】C13H10F2O 【 分 子 量 】220.2186064 【元素组成】C 70.9% H 4.58% F 17.25% O 7.27% |
合成路线1
该中间体在本合成路线中的序号：(IV)1-(3-Phenylpropyl)piperazine (III) has been obtained by condensation of 3-phenylpropyl bromide (I) with piperazine (II) in refluxing acetonitrile. The condensation of bis(4-fluorophenyl)methanol (IV) with 2-chloroethanol (V) by means of sulfuric acid gives the 2-chloroethyl bis(4-fluorophenyl)methyl ether (VI), which si treated with NaI to yield the corresponding iodo derivative (VII). Finally this compound is condensed with the intermediate piperazine (III) by means of aq. Na2CO3 to afford the target disubstituted piperazine.
| 【1】 Zhang, J.; Ironside, M.D.; Sugathapala, P.M.; Robertson, J.; Darey, M.C.P.; Scale-up synthesis of the dopamine uptake inhibitor GBR-12909. Org Process Res Dev 2002, 6, 5, 621. |
| 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) | 20884 | 1-(3-bromopropyl)benzene | 637-59-2 | C9H11Br | 详情 | 详情 |
| (II) | 10355 | Diethylenediamine; Piperazine | 110-85-0 | C4H10N2 | 详情 | 详情 |
| (III) | 38636 | 1-(3-phenylpropyl)piperazine | C13H20N2 | 详情 | 详情 | |
| (IV) | 41974 | 4,4'-Difluorobenzhydrol; bis(4-Fluorophenyl)methanol; alpha-(4-fluorophenyl)benzenemethanol; 4-fluoro-alpha-(4-fluorophenyl)benzenemethanol | 365-24-2 | C13H10F2O | 详情 | 详情 |
| (V) | 10384 | 2-Chloro-1-ethanol; Ethylene chlorohydrin | 107-07-3 | C2H5ClO | 详情 | 详情 |
| (VI) | 54931 | 1-[(2-chloroethoxy)(4-fluorophenyl)methyl]-4-fluorobenzene; bis(4-fluorophenyl)methyl 2-chloroethyl ether | C15H13ClF2O | 详情 | 详情 | |
| (VII) | 56868 | bis(4-fluorophenyl)methyl 2-iodoethyl ether; 1-fluoro-4-[(4-fluorophenyl)(2-iodoethoxy)methyl]benzene | C15H13F2IO | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)The precursor bromoether (III) was prepared by condensation of 4,4’-difluorobenzhydrol (I) with 2-bromoethanol (II) under acidic conditions. Treatment of 4-bromocinnamic acid (IV) with thionyl chloride afforded acid chloride (V), which was coupled with ethylenediamine (VI) to furnish mono amide (VII). The title compound was finally obtained by alkylation of amine (VII) with bromide (III) in the presence of K2CO3.
| 【1】 Elmaleh, D.R.; Fischman, A.J.; Hanson, R.N.; Choi, S.-W.; Design, synthesis, and biological evaluation of novel non-piperazine analogues of 1-[2-(diphenylmethoxy]ethyl]- and 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]4-(3-phenylpropyl)piperazines as dopamine transporter inhibitors. J Med Chem 1999, 42, 18, 3647. |
| 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) | 41974 | 4,4'-Difluorobenzhydrol; bis(4-Fluorophenyl)methanol; alpha-(4-fluorophenyl)benzenemethanol; 4-fluoro-alpha-(4-fluorophenyl)benzenemethanol | 365-24-2 | C13H10F2O | 详情 | 详情 |
| (II) | 10059 | Ethylene bromohydrin; 2-Bromo-1-ethanol | 540-51-2 | C2H5BrO | 详情 | 详情 |
| (III) | 41975 | 1-[(2-bromoethoxy)(4-fluorophenyl)methyl]-4-fluorobenzene; bis(4-fluorophenyl)methyl 2-bromoethyl ether | C15H13BrF2O | 详情 | 详情 | |
| (IV) | 41976 | (E)-3-(4-bromophenyl)-2-propenoic acid | C9H7BrO2 | 详情 | 详情 | |
| (V) | 41977 | (E)-3-(4-bromophenyl)-2-propenoyl chloride | C9H6BrClO | 详情 | 详情 | |
| (VI) | 14754 | ethylenediamine;1,2-Diaminoethane;ethane-1,2-diamine；1,2-Ethanediamine | 107-15-3 | C2H8N2 | 详情 | 详情 |
| (VII) | 41978 | (E)-N-(2-aminoethyl)-3-(4-bromophenyl)-2-propenamide | C11H13BrN2O | 详情 | 详情 |