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【结 构 式】 
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【分子编号】16790 【品名】4-(4-fluorobenzyl)piperidine hydrochloride 【CA登记号】92822-02-1 |
【 分 子 式 】C12H17ClFN 【 分 子 量 】229.7248232 【元素组成】C 62.74% H 7.46% Cl 15.43% F 8.27% N 6.1% |
合成路线1
该中间体在本合成路线中的序号：(III)The overall synthetic approach to eliprodil hydrochloride is shown in Scheme 21238101a: 1-Acetylpiperidine-4-carboxylic acid (I) is converted into its acid chloride and reacted with fluorobenzene in the presence of aluminum chloride to give the ketone (II). Wolff-Kishner reduction of the ketone (II) affords 4-[(4-fluorophenyl)methyl]piperidine (III), which is purified by distillation and isolated as its hydrochloride salt. Condensation of the piperidine derivate (III) (as the free base) with 2-bromo-1-(4-chlorophenyl)ethanone (IV) in the presence of potassium carbonate yields the aminoketone which is isolated as its hydrochloride salt (V). Reduction of (V) with potassium borohydride and salification of the resulting base with anhydrous hydrogen chloride in ether provides eliprodil hydrochloride (VI), which is purified by recrystallization.
| 【1】 Wick, A.; Frost, J.; Gaudilliere, B.; Bertin, J.; Dupont, R.; Rousseau, J. (Sanofi-Synthelabo ); 1-Phenyl-2-piperidino propanol derivs., their preparation and medicines containing them. EP 0109317 . |
| 【2】 Benavides, J.; Scatton, B.; Carter, C.; George, P.; Frost, J.; Thenot, J.P.; Giroux, C.; Eliprodil Hydrochloride. Drugs Fut 1994, 19, 10, 905. |
| 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) | 16788 | 1-acetyl-4-piperidinecarboxylic acid | 25503-90-6 | C8H13NO3 | 详情 | 详情 |
| (II) | 16789 | 1-[4-(4-fluorobenzoyl)piperidino]-1-ethanone | C14H16FNO2 | 详情 | 详情 | |
| (III) | 16790 | 4-(4-fluorobenzyl)piperidine hydrochloride | 92822-02-1 | C12H17ClFN | 详情 | 详情 |
| (IV) | 16720 | 2-bromo-1-(4-chlorophenyl)-1-ethanone; 2-Bromo-4'-chloroacetophenone | 536-38-9 | C8H6BrClO | 详情 | 详情 |
| (V) | 16792 | 1-(4-chlorophenyl)-2-[4-(4-fluorobenzyl)-1-piperidinyl]-1-ethanone hydrochloride | C20H22Cl2FNO | 详情 | 详情 |