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【结 构 式】 
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【分子编号】36936 【品名】6-bromo-2,2-dimethyl-4H-1,3-benzodioxine 【CA登记号】 |
【 分 子 式 】C10H11BrO2 【 分 子 量 】243.10014 【元素组成】C 49.41% H 4.56% Br 32.87% O 13.16% |
合成路线1
该中间体在本合成路线中的序号：(IX)The reaction of 4-phenyl-1-butanol (I) with 1,6-dibromohexane (II) by means of KOH and tetrabutylammonium bisulfate gives the butyl hexyl ether (III), which is condensed with 2-aminoacetaldehyde dimethylacetal (IV) in refluxing toluene yielding 2-[6-(4-phenylbutoxy)hexylamino]acetaldehyde dimethylacetal (V). The protection of the amino group of (V) with N-(benzyloxycarbonyloxy)succinimide and triethylamine in acetone affords the carbamate (VI), which is treated with TsOH in acetone to provide the acetaldehyde derivative (VII). The condensation of (VII) with 6-bromo-2,2-dimethyl-1,3-benzodioxan (VIII) (obtained by cyclization of phenol (IX) with acetone and AlCl3) by means of Mg in THF gives the expected carbinol (X), which is deprotected with H2 over Pd/C in methanol yielding the aminoethanol derivative (XI). Finally, this compound is treated with HCl in methanol/water to open the 1,3-dioxane ring and afford the target compound.
| 【1】 Marquillas Olondriz, F.; Dalmases Barjoan, P.; Bessa Bellmunt, J. (Laboratorios Vita, SA); New derivs. of 6-(4-phenylbutoxy)hexylamine and process for producing salmeterol. ES 2142771; WO 0018722 . |
| 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) | 27291 | 4-phenyl-1-butanol | 3360-41-6 | C10H14O | 详情 | 详情 |
| (II) | 24786 | 1,6-dibromohexane | 629-03-8 | C6H12Br2 | 详情 | 详情 |
| (III) | 31479 | 1-[4-[(6-bromohexyl)oxy]butyl]benzene; 6-bromohexyl-4-phenylbutyl ether; 6-Bromohexyloxybutylbenzene | 94749-73-2 | C16H25BrO | 详情 | 详情 |
| (IV) | 34158 | aminoacetaldehyde dimethylacetal; 2,2-dimethoxy-1-ethanamine; 2,2-dimethoxyethylamine | 22483-09-6 | C4H11NO2 | 详情 | 详情 |
| (V) | 36932 | N-(2,2-dimethoxyethyl)-N-[6-(4-phenylbutoxy)hexyl]amine; N-(2,2-dimethoxyethyl)-6-(4-phenylbutoxy)-1-hexanamine | C20H35NO3 | 详情 | 详情 | |
| (VI) | 36933 | benzyl 2,2-dimethoxyethyl[6-(4-phenylbutoxy)hexyl]carbamate | C28H41NO5 | 详情 | 详情 | |
| (VII) | 36934 | benzyl 2-oxoethyl[6-(4-phenylbutoxy)hexyl]carbamate | C26H35NO4 | 详情 | 详情 | |
| (VIII) | 36935 | 4-bromo-2-(hydroxymethyl)phenol | 2316-64-5 | C7H7BrO2 | 详情 | 详情 |
| (IX) | 36936 | 6-bromo-2,2-dimethyl-4H-1,3-benzodioxine | C10H11BrO2 | 详情 | 详情 | |
| (X) | 36937 | benzyl 2-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-hydroxyethyl[6-(4-phenylbutoxy)hexyl]carbamate | C36H47NO6 | 详情 | 详情 | |
| (XI) | 36938 | 1-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-[[6-(4-phenylbutoxy)hexyl]amino]-1-ethanol | C28H41NO4 | 详情 | 详情 |