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【结 构 式】 
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【分子编号】42345 【品名】1-(benzyloxy)-2-[(E)-2-(3-methoxyphenyl)ethenyl]benzene; benzyl 2-[(E)-2-(3-methoxyphenyl)ethenyl]phenyl ether 【CA登记号】 |
【 分 子 式 】C22H20O2 【 分 子 量 】316.3996 【元素组成】C 83.52% H 6.37% O 10.11% |
合成路线1
该中间体在本合成路线中的序号：(VII)Synthesis of intermediate (VIII): Condensation of salicyl alcohol (I) with benzyl bromide (II) by means of KOtBu in DMF gives 2-benzyloxybenzyl alcohol (III), which is converted into chloride (IV) by reaction with SOCl2 in THF. Treatment of derivative (IV) with PPh3 in refluxing toluene furnishes triphenylphosphonium chloride (V), which is condensed with aldehyde (VI) by means of DBU in acetonitrile to afford benzyloxystilbene derivative (VII). Finally, intermediate (VIII) is obtained by hydrogenation of (VII) over Pd/C in EtOH.
| 【1】 Fujimoto, K.; Tanaka, N.; Asai, F.; Ito, T.; Koike, H. (Sankyo Co., Ltd.); Phenoxyalkylamines, -pyrrolidines and -piperidines for the treatment and prevention of circulatory diseases and psychosis. EP 0600717; JP 1994234736; JP 1994306025; US 5556864 . |
| 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) | 42341 | 2-(hydroxymethyl)phenol | 90-01-7 | C7H8O2 | 详情 | 详情 |
| (II) | 12912 | 1-(Bromomethyl)benzene; Alpha-bromotoluene | 100-39-0 | C7H7Br | 详情 | 详情 |
| (III) | 42342 | [2-(benzyloxy)phenyl]methanol | C14H14O2 | 详情 | 详情 | |
| (IV) | 42343 | benzyl 2-(chloromethyl)phenyl ether; 1-(benzyloxy)-2-(chloromethyl)benzene | C14H13ClO | 详情 | 详情 | |
| (V) | 42344 | [2-(benzyloxy)benzyl](triphenyl)phosphonium chloride | C32H28ClOP | 详情 | 详情 | |
| (VI) | 20589 | 3-methoxybenzaldehyde; m-Anisaldehyde | 591-31-1 | C8H8O2 | 详情 | 详情 |
| (VII) | 42345 | 1-(benzyloxy)-2-[(E)-2-(3-methoxyphenyl)ethenyl]benzene; benzyl 2-[(E)-2-(3-methoxyphenyl)ethenyl]phenyl ether | C22H20O2 | 详情 | 详情 | |
| (VIII) | 13604 | 2-(3-Methoxyphenethyl)phenol | C15H16O2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VII)Treatment of salicyl alcohol (I) with benzyl bromide (II) in DMF in the presence of KOtBu affords benzyloxybenzyl alcohol (III), which is converted into its chloride form (IV) by means of SOCl2 in THF. Reaction of (IV) with PPh3 in refluxing toluene gives triphenyl phosphonium chloride derivative (V), which is then subjected to a Wittig reaction with aldehyde (VI) to yield olefine (VII). Catalytic hydrogenolysis of (VII) over Pd/C provides phenol derivative (VIII), which is then alkylated by reaction with tosylate (XVI) and KOtBu in dimethylacetamide to yield (XVII). Finally, ethoxycarbonyl derivative (XVII) is reduced by means of LiAlH4 in THF and converted into its hydrochloride form by treatment with HCl in dioxane. Intermediate (XVI) can be prepared as follows: Protection of 2(S)-pyrrolidinemethanol (IX) by reaction with ethyl chloroformate in the presence of Et3N in dichloromethane affords carbamate (XI), which is tosylated by means of Ts2O and Et3N in dichloromethane to yield (XII). One carbon elongation of (XII) by reaction with NaCN in DMF provides (XIII), which is then converted into ester (XIV) by means of H2SO4 in EtOH. Reduction of ester (XIV) with LiAlH4 in THF gives alcohol (XV), which is finally tosylated by reaction with Ts2O and Et3N in dichloromethane.
| 【1】 Fujimoto, K.; Tanaka, N.; Asai, F.; Ito, T.; Koike, H. (Sankyo Co., Ltd.); Phenoxyalkylamines, -pyrrolidines and -piperidines for the treatment and prevention of circulatory diseases and psychosis. EP 0600717; JP 1994234736; JP 1994306025; US 5556864 . |
| 【2】 Goto, R.; Hayakawa, M.; Ito, R.; Ogawa, T.; Sugidachi, A.; Tanaka, N.; Asai, F.; Fujimoto, K.; [2-(omega-Phenylalkyl)phenoxy]alkylamines II: Synthesis and selective serotonin-2 receptor binding. Chem Pharm Bull 2000, 48, 2, 245. |
| 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) | 42341 | 2-(hydroxymethyl)phenol | 90-01-7 | C7H8O2 | 详情 | 详情 |
| (II) | 12912 | 1-(Bromomethyl)benzene; Alpha-bromotoluene | 100-39-0 | C7H7Br | 详情 | 详情 |
| (III) | 42342 | [2-(benzyloxy)phenyl]methanol | C14H14O2 | 详情 | 详情 | |
| (IV) | 42343 | benzyl 2-(chloromethyl)phenyl ether; 1-(benzyloxy)-2-(chloromethyl)benzene | C14H13ClO | 详情 | 详情 | |
| (V) | 42344 | [2-(benzyloxy)benzyl](triphenyl)phosphonium chloride | C32H28ClOP | 详情 | 详情 | |
| (VI) | 20589 | 3-methoxybenzaldehyde; m-Anisaldehyde | 591-31-1 | C8H8O2 | 详情 | 详情 |
| (VII) | 42345 | 1-(benzyloxy)-2-[(E)-2-(3-methoxyphenyl)ethenyl]benzene; benzyl 2-[(E)-2-(3-methoxyphenyl)ethenyl]phenyl ether | C22H20O2 | 详情 | 详情 | |
| (VIII) | 13604 | 2-(3-Methoxyphenethyl)phenol | C15H16O2 | 详情 | 详情 | |
| (IX) | 21347 | (2S)pyrrolidinylmethanol | 23356-96-9 | C5H11NO | 详情 | 详情 |
| (X) | 11229 | 1-[(Chlorocarbonyl)oxy]ethane;ethyl carbonochloridate; Carbonchloridic acid ethyl ester;Ethyl chloroformate;Ethyl chlorocarbonate | 541-41-3 | C3H5ClO2 | 详情 | 详情 |
| (XI) | 42346 | ethyl (2S)-2-(hydroxymethyl)-1-pyrrolidinecarboxylate | C8H15NO3 | 详情 | 详情 | |
| (XII) | 42347 | ethyl (2S)-2-([[(4-methylphenyl)sulfonyl]oxy]methyl)-1-pyrrolidinecarboxylate | C15H21NO5S | 详情 | 详情 | |
| (XIII) | 42348 | ethyl (2S)-2-(cyanomethyl)-1-pyrrolidinecarboxylate | C9H14N2O2 | 详情 | 详情 | |
| (XIV) | 42349 | ethyl (2S)-2-(2-ethoxy-2-oxoethyl)-1-pyrrolidinecarboxylate | C11H19NO4 | 详情 | 详情 | |
| (XV) | 42350 | ethyl (2S)-2-(2-hydroxyethyl)-1-pyrrolidinecarboxylate | C9H17NO3 | 详情 | 详情 | |
| (XVI) | 42351 | ethyl (2S)-2-(2-[[(4-methylphenyl)sulfonyl]oxy]ethyl)-1-pyrrolidinecarboxylate | C16H23NO5S | 详情 | 详情 | |
| (XVII) | 42352 | ethyl (2S)-2-[2-[2-(3-methoxyphenethyl)phenoxy]ethyl]-1-pyrrolidinecarboxylate | C24H31NO4 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(VII)Synthesis of intermediate (VIII): Condensation of salicyl alcohol (I) with benzyl bromide (II) by means of KOtBu in DMF gives 2-benzyloxybenzyl alcohol (III), which is then converted into chloride (IV) by reaction with SOCl2 in THF. Treatment of derivative (IV) with PPh3 in refluxing toluene furnishes triphenylphosphonium chloride (V), which is then condensed with aldehyde (VI) by means of DBU in acetonitrile to afford benzyloxystilbene derivative (VII). Finally, intermediate (VIII) is obtained by hydrogenation of (VII) over Pd/C in EtOH.
| 【1】 Fujimoto, K.; Tanaka, N.; Asai, F.; Ito, T.; Koike, H. (Sankyo Co., Ltd.); Phenoxyalkylamines, -pyrrolidines and -piperidines for the treatment and prevention of circulatory diseases and psychosis. EP 0600717; JP 1994234736; JP 1994306025; US 5556864 . |
| 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) | 42341 | 2-(hydroxymethyl)phenol | 90-01-7 | C7H8O2 | 详情 | 详情 |
| (II) | 12912 | 1-(Bromomethyl)benzene; Alpha-bromotoluene | 100-39-0 | C7H7Br | 详情 | 详情 |
| (III) | 42342 | [2-(benzyloxy)phenyl]methanol | C14H14O2 | 详情 | 详情 | |
| (IV) | 42343 | benzyl 2-(chloromethyl)phenyl ether; 1-(benzyloxy)-2-(chloromethyl)benzene | C14H13ClO | 详情 | 详情 | |
| (V) | 42344 | [2-(benzyloxy)benzyl](triphenyl)phosphonium chloride | C32H28ClOP | 详情 | 详情 | |
| (VI) | 20589 | 3-methoxybenzaldehyde; m-Anisaldehyde | 591-31-1 | C8H8O2 | 详情 | 详情 |
| (VII) | 42345 | 1-(benzyloxy)-2-[(E)-2-(3-methoxyphenyl)ethenyl]benzene; benzyl 2-[(E)-2-(3-methoxyphenyl)ethenyl]phenyl ether | C22H20O2 | 详情 | 详情 | |
| (VIII) | 13604 | 2-(3-Methoxyphenethyl)phenol | C15H16O2 | 详情 | 详情 |