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【结 构 式】 
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【分子编号】17396 【品名】1-(4-fluorophenethyl)-4-piperidinecarbonitrile 【CA登记号】 |
【 分 子 式 】C14H17FN2 【 分 子 量 】232.3008632 【元素组成】C 72.39% H 7.38% F 8.18% N 12.06% |
合成路线1
该中间体在本合成路线中的序号：(IV)MDL-100907 can be obtained by several different ways: 1) The condensation of piperidine-4-carboxamide (I) with 2-(4-fluorophenyl)ethyl bromide (II) by means of K2CO3 in hot DMF gives 1-[2-(4-fluorophenyl)ethyl]piperidine-4-carboxamide (III), which by reaction with refluxing POCl3 is converted into the nitrile (IV). The reduction of (IV) with diisobutyl aluminum hydride (DIBAL) in THF affords the aldehyde (V), which by condensation with 1,2-dimethoxybenzene (veratrole) (VI) by means of BuLi in THF affords racemic MDL-100907 (VII). The esterification of (VII) with (S)-2-methoxy-2-phenylacetic acid (VIII) by means of dicyclohexylcarbodiimide (DCC) and dimethyl-aminopyridine (DMAP) in refluxing CHCl3 affords a mixture of diastereomers that is submitted to column chromatography over silica gel to afford the pure diastereomer (IX). Finally, (IX) is saponified with K2CO3 in methanol/ water
| 【1】 Castaner, J.; Sorbera, L.A.; Silvestre, J.S.; MDL-100907. Drugs Fut 1998, 23, 9, 955. |
| 【2】 Carr, A.A.; Kane, J.M.; Hay, D.A. (Merrell Pharmaceuticals, Inc.); (+)-*-(2,3-Dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol. EP 0531410; JP 1993507482; US 5134149; WO 9118602 . |
| 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) | 11762 | 4-Piperidinecarboxamide; Isonipecotamide | 39546-32-2 | C6H12N2O | 详情 | 详情 |
| (II) | 17394 | 1-(2-bromoethyl)-4-fluorobenzene | C8H8BrF | 详情 | 详情 | |
| (III) | 17395 | 1-(4-fluorophenethyl)-4-piperidinecarboxamide | C14H19FN2O | 详情 | 详情 | |
| (IV) | 17396 | 1-(4-fluorophenethyl)-4-piperidinecarbonitrile | C14H17FN2 | 详情 | 详情 | |
| (V) | 17397 | 1-(4-fluorophenethyl)-4-piperidinecarbaldehyde | C14H18FNO | 详情 | 详情 | |
| (VI) | 17398 | 2-methoxyphenyl methyl ether; Veratrole; 1,2-dimethoxybenzene | 91-16-7 | C8H10O2 | 详情 | 详情 |
| (VII) | 17399 | (2,3-dimethoxyphenyl)[1-(4-fluorophenethyl)-4-piperidinyl]methanol | C22H28FNO3 | 详情 | 详情 | |
| (VIII) | 17400 | (2S)-2-methoxy-2-phenylethanoic acid | C9H10O3 | 详情 | 详情 | |
| (IX) | 17401 | (R)-(2,3-dimethoxyphenyl)[1-(4-fluorophenethyl)-4-piperidinyl]methyl (2S)-2-methoxy-2-phenylethanoate | C31H36FNO5 | 详情 | 详情 |