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【结 构 式】 
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【分子编号】41223 【品名】5-(benzyloxy)-2,2,4,6,7-pentamethyl-3-methylene-2,3-dihydro-1-benzofuran; benzyl 2,2,4,6,7-pentamethyl-3-methylene-2,3-dihydro-1-benzofuran-5-yl ether 【CA登记号】 |
【 分 子 式 】C21H24O2 【 分 子 量 】308.42036 【元素组成】C 81.78% H 7.84% O 10.38% |
合成路线1
该中间体在本合成路线中的序号：(VI)The cyclization of 2,5-dimethoxy-1,3,4-trimethylbenzene (I) with 2-bromo-2-methylpropionyl bromide (II) by means of FeCl3 and NaOH in methanol/water gives 5-hydroxy-2,2,4,6,7-pentamethyl-2,3-dihydrobenzofuran-3-one (III), which is treated with benzyl bromide (IV) and K2CO3 to yield the benzyl ether (V). The reaction of (V) with methylmagnesium bromide, followed by dehydration of the intermediate carbinol affords the methylene derivative (VI), which is hydroxylated with borane / dimethylsulfide and NaOH/H2O2 to furnish the hydroxymethyl compound (VII). The reaction of (VII) with MsCl and TEA gives the mesylate (VIII), which is finally condensed with 1-methylpiperazine (IX) by means of K2CO3 and debenzylated by hydrogenation with H2 over Pd/C in ethanol/HOAc to afford the target compound as a racemic mixture.
| 【1】 Petty, M.A.; Marciniak, G.; Design and biological evaluation of new antioxidants for use in cerebrovascular disorders. Drugs Fut 1996, 21, 10, 1037. |
| 【2】 Ayers, T.A.; Schnettler, R.A.; Marciniak, G.; Krysan, D.J. (Hoechst Marion Roussel Inc.); Novel process for preparing derivatives of 2,2,4,6,7-pentaalkyl-2,2-dihydrobenzofuranols. EP 0813530 . |
| 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) | 41220 | 1,4-dimethoxy-2,3,5-trimethylbenzene; 4-methoxy-2,3,5-trimethylphenyl methyl ether | C11H16O2 | 详情 | 详情 | |
| (II) | 19367 | 2-bromo-2-methylpropanoyl bromide | 20769-85-1 | C4H6Br2O | 详情 | 详情 |
| (III) | 41221 | 5-hydroxy-2,2,4,6,7-pentamethyl-1-benzofuran-3(2H)-one | C13H16O3 | 详情 | 详情 | |
| (IV) | 12912 | 1-(Bromomethyl)benzene; Alpha-bromotoluene | 100-39-0 | C7H7Br | 详情 | 详情 |
| (V) | 41222 | 5-(benzyloxy)-2,2,4,6,7-pentamethyl-1-benzofuran-3(2H)-one | C20H22O3 | 详情 | 详情 | |
| (VI) | 41223 | 5-(benzyloxy)-2,2,4,6,7-pentamethyl-3-methylene-2,3-dihydro-1-benzofuran; benzyl 2,2,4,6,7-pentamethyl-3-methylene-2,3-dihydro-1-benzofuran-5-yl ether | C21H24O2 | 详情 | 详情 | |
| (VII) | 30773 | [5-(benzyloxy)-2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-3-yl]methanol | C21H26O3 | 详情 | 详情 | |
| (VIII) | 26455 | 5-(benzyloxy)-2,2,4,6,7-pentamethyl-3-([[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]methyl)-2,3-dihydro-1-benzofuran | C24H32O3S | 详情 | 详情 | |
| (IX) | 10061 | 1-Methylpiperazine; 1-Methyl piperazine; N-Methylpiperazine | 109-01-3 | C5H12N2 | 详情 | 详情 |