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【结 构 式】 
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【分子编号】40495 【品名】2-[(R)-[1-(4-fluorophenethyl)-4-piperidinyl](hydroxy)methyl]-6-methoxyphenol 【CA登记号】 |
【 分 子 式 】C21H26FNO3 【 分 子 量 】359.4407832 【元素组成】C 70.17% H 7.29% F 5.29% N 3.9% O 13.35% |
合成路线1
该中间体在本合成路线中的序号：(XI)The synthesis of MDL-100907 [11C]-labeled at the 2'-methoxy group has been reported: Condensation of 2-(4-fluorophenyl)ethyl bromide (I) with piperidine-4-carboxylic acid ethyl ester (II) by means of K2CO3 in DMF gives 1-[2-(4-fluorophenyl)ethyl]piperidine-4-carboxylic acid ethyl ester (III), which is treated with N,O-dimethylhydroxylamine and ethylmagnesium bromide in THF to yield compound (IV). Condensation of (IV) with veratrole (V) by means of BuLi in THF affords the 4-benzoylpiperidine derivative (VI), which is reduced with NaBH4 in methanol to give the racemic carbinol (VII). Optical resolution of (VII) by esterification with (S)-2-methoxy-2-phenylacetic acid (VIII) by means of DCC and DMAP in chloroform followed by column chromatography yields the diastereomer (IX), which is hydrolyzed with K2CO3 in methanol to afford MDL-100907 (X). Selective demethylation of (X) with L-selectride in THF gives the 2'-hydroxy derivative (XI), which is finally remethylated with [11C]-methyl iodide and K2CO3 in methanol.
| 【1】 Mathis, C.A.; Huang, Y.Y.; Mahmood, K.; An efficient synthesis of the precursors of [11C]MDL 100907 labeled in two specific positions. J Label Compd Radiopharm 1999, 42, 10, 949. |
| 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) | 17394 | 1-(2-bromoethyl)-4-fluorobenzene | C8H8BrF | 详情 | 详情 | |
| (II) | 17410 | Ethyl isonipecotate; ethyl 4-piperidinecarboxylate | 1126-09-6 | C8H15NO2 | 详情 | 详情 |
| (III) | 17411 | ethyl 1-(4-fluorophenethyl)-4-piperidinecarboxylate | C16H22FNO2 | 详情 | 详情 | |
| (IV) | 17412 | 1-(4-fluorophenethyl)-N-methoxy-N-methyl-4-piperidinecarboxamide | C16H23FN2O2 | 详情 | 详情 | |
| (V) | 40496 | tert-butyl(2-methoxyphenoxy)diphenylsilane; tert-butyl(diphenyl)silyl 2-methoxyphenyl ether | C23H26O2Si | 详情 | 详情 | |
| (VI) | 17409 | (2,3-dimethoxyphenyl)[1-(4-fluorophenethyl)-4-piperidinyl]methanone | C22H26FNO3 | 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 | |
| (X) | 40494 | (R)-(2,3-dimethoxyphenyl)[1-(4-fluorophenethyl)-4-piperidinyl]methanol | C22H28FNO3 | 详情 | 详情 | |
| (XI) | 40495 | 2-[(R)-[1-(4-fluorophenethyl)-4-piperidinyl](hydroxy)methyl]-6-methoxyphenol | C21H26FNO3 | 详情 | 详情 |