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【结 构 式】 
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【分子编号】16838 【品名】1-Bis(4-fluorophenyl)methyl piperazine; 1-[bis(4-fluorophenyl)methyl]piperazine 【CA登记号】27469-60-9 |
【 分 子 式 】C17H18F2N2 【 分 子 量 】288.3402064 【元素组成】C 70.81% H 6.29% F 13.18% N 9.72% |
合成路线1
该中间体在本合成路线中的序号：(I)By reductocondensation of 2,3,4-trimethoxybenzaldehyde (I) with l-[bis(4-fluorophenyl)methyl] piperazine (II) by means of formic acid at 100-120 C.
| 【1】 Stukamoto, G.; Kanazawa, T.; Ohtaka, H.; Ito, K.; Benzylpiperazine derivatives. IV. Synthesis and ce. Chem Pharm Bull 1987, 35, 8, 3270. |
| 【2】 Ito, K.; Kanazawa, T.; Ohtaka, H.; Tsukamoto, G. (Kanebo Pharmaceuticals, Ltd.); 1-(2,3,4-Tri-methoxybenzyl)-4[bis(4-fluorophenyl)m. EP 0159566; ES 8702393; ES 8801236; ES 8801237; JP 1985222472; US 4663325 . |
| 【3】 Prous, J.; Castaner, J.; KB-2796. Drugs Fut 1988, 13, 4, 312. |
合成路线2
该中间体在本合成路线中的序号：(I)Efletirizine can be obtained by two similar ways: 1) The condensation of 1-[bis(4-fluorophenyl)methyl]piperazine (I) with 2-(2-chloroethoxy)acetamide (II) by means of Na2CO3 in hot xylene gives 2-[2-[4-[bis(4-fluorophenyl)methyl]piperazin-1-yl]ethoxy]acetamide (III), which is then hydrolyzed with 4N NaOH in refluxing ethanol. 2) The condensation of 1-[bis(4-fluorophenyl)methyl]piperazine (I) with 2-(2-chloroethoxy)acetic acid methyl ester (IV) by means of Na2CO3 in hot xylene gives 2-[2-[4-[bis(4-fluorophenyl)methyl]piperazin-1-yl]ethoxy]acetic acid methyl ester amide (V), which is then hydrolyzed with 1N KOH in refluxing ethanol.
| 【1】 Graul, A.; Leeson, P.; Castañer, R.M.; Efletirizine. Drugs Fut 1997, 22, 6, 626. |
| 【2】 Baltes, E.; De Lannoy, J.; Rodriguez, L. (UCB SA); Novel 2-[4-(diphenylmethyl)-1-piperazinyl]acetic acids and their amides, process for their preparation and pharmaceutical compsns. Containing them. EP 0058146; US 4525358 . |
| 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) | 16838 | 1-Bis(4-fluorophenyl)methyl piperazine; 1-[bis(4-fluorophenyl)methyl]piperazine | 27469-60-9 | C17H18F2N2 | 详情 | 详情 |
| (II) | 16839 | 2-(2-chloroethoxy)acetamide | C4H8ClNO2 | 详情 | 详情 | |
| (III) | 16840 | 2-(2-[4-[bis(4-fluorophenyl)methyl]piperazino]ethoxy)acetamide | C21H25F2N3O2 | 详情 | 详情 | |
| (IV) | 16841 | methyl 2-(2-chloroethoxy)acetate | C5H9ClO3 | 详情 | 详情 | |
| (V) | 16842 | methyl 2-(2-[4-[bis(4-fluorophenyl)methyl]piperazino]ethoxy)acetate | C22H26F2N2O3 | 详情 | 详情 |