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【结 构 式】 
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【药物名称】 【化学名称】4-[1-(4-Phenylbutyl)piperidin-4-yl]phenol 【CA登记号】 【 分 子 式 】C21H27NO 【 分 子 量 】309.45544 |
【开发单位】Pfizer (Originator) 【药理作用】Antiepileptic Drugs, Cerebrovascular Diseases, Treatment of, NEUROLOGIC DRUGS, Stroke, Treatment of, NMDA Antagonists |
合成路线1
The alkylation of 4-(4-methoxyphenyl)piperidine (I) with 4-phenylbutyl tosylate (II) provided the tertiary amine (III). The methyl ether group of (III) was then cleaved using BBr3 to furnish the title phenol.
| 【1】 Bigge, C.F.; Cai, S.X.; Weber, E.; Woodward, R.; Keana, J.F.W.; Lan, N.C.; Guzikowski, A.P.; Zhou, Z.-L.; Yeun, P.-W. (CoCensys, Inc.; Pfizer Inc.); 4-Substd. piperidine analogs and their use as subtype selective NMDA receptor antagonists. EP 0869792; JP 2000500773; WO 9723216 . |
| 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) | 43153 | 4-(4-methoxyphenyl)piperidine; methyl 4-(4-piperidinyl)phenyl ether | 67259-62-5 | C12H17NO | 详情 | 详情 |
| (II) | 43154 | 4-phenylbutyl 4-methylbenzenesulfonate | C17H20O3S | 详情 | 详情 | |
| (III) | 43155 | 4-(4-methoxyphenyl)-1-(4-phenylbutyl)piperidine; methyl 4-[1-(4-phenylbutyl)-4-piperidinyl]phenyl ether | C22H29NO | 详情 | 详情 |
合成路线2
In an alternative procedure, lithiation of 4-(benzyloxy)-1-bromobenzene (IV), followed by addition of 1-benzyl-4-piperidone (V), gave piperidinol (VI). Subsequent treatment of (VI) with HCl produced dehydration of the tertiary alcohol and benzyl ether cleavage to give (VII). Double bond reduction and hydrogenolysis of the N-benzyl group of (VII) with H2 over Pd/C gave 4-(4-hydroxyphenyl)piperidine (VIII). This was finally alkylated with tosylate (II) to yield the title compound.
| 【1】 Guzikowski, A.P.; Acosta-Burruel, M.; Tamiz, A.P.; et al.; Synthesis of N-substituted 4-(4-hydroxyphenyl)piperidines, 4-(4-hydroxybenzyl)piperidines, and (±)-3-(4-hydroxyphenyl)pyrrolidines: Selective antagonists at the 1A/2B NMDA receptor subtype. J Med Chem 2000, 43, 5, 984. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (II) | 43154 | 4-phenylbutyl 4-methylbenzenesulfonate | C17H20O3S | 详情 | 详情 | |
| (IV) | 43156 | 1-(benzyloxy)-4-bromobenzene; benzyl 4-bromophenyl ether | 6793-92-6 | C13H11BrO | 详情 | 详情 |
| (V) | 15720 | 1-benzyltetrahydro-4(1H)-pyridinone; 1-Benzyl-4-piperidone; N-Benzyl-4-piperidone; 1-(benzyl)-4-piperidinone; 1-benzylpiperidin-4-one; 1-(benzyl)piperidin-4-one | 3612-20-2 | C12H15NO | 详情 | 详情 |
| (VI) | 43157 | 1-benzyl-4-[4-(benzyloxy)phenyl]-4-piperidinol | C25H27NO2 | 详情 | 详情 | |
| (VII) | 43158 | 4-(1-benzyl-1,2,3,6-tetrahydro-4-pyridinyl)phenol | C18H19NO | 详情 | 详情 | |
| (VIII) | 43159 | 4-(4-piperidinyl)phenol | C11H15NO | 详情 | 详情 |