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【结 构 式】 
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【分子编号】50874 【品名】5-(2-[benzyl[6-(4-phenylbutoxy)hexyl]amino]acetyl)-2-hydroxybenzaldehyde 【CA登记号】 |
【 分 子 式 】C32H39NO4 【 分 子 量 】501.666 【元素组成】C 76.62% H 7.84% N 2.79% O 12.76% |
合成路线1
该中间体在本合成路线中的序号：(III)The condensation of N-benzyl-N-[6-(4-phenylbutoxy)hexyl]amine (I) with 5-(bromoacetyl)salicylaldehyde (II) by means of TEA in isopropanol gives the adduct (III), which is debenzylated and reduced with H2 over Pt/C and Pd/C in ethanol to afford the target triol.
| 【1】 Ariza Aranda, J.; Serra Masià, J.; Montserrat Vidal, C. (Laboratorios Salvat SA); 6-[4-(Phenylbutoxy)]hexylaminomethyl-4-hydroxy-alpha1,alpha3-benzenedimethanol. Process for obtaining it and novel intermediates for its preparation. ES 2065269 . |
| 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) | 35837 | N-benzyl-6-(4-phenylbutoxy)-1-hexanamine; N-benzyl-N-[6-(4-phenylbutoxy)hexyl]amine | C23H33NO | 详情 | 详情 | |
| (II) | 50873 | 5-(2-bromoacetyl)-2-hydroxybenzaldehyde | C9H7BrO3 | 详情 | 详情 | |
| (III) | 50874 | 5-(2-[benzyl[6-(4-phenylbutoxy)hexyl]amino]acetyl)-2-hydroxybenzaldehyde | C32H39NO4 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VII)The condensation of 4-phenyl-1-butanol (I) with 1,6-dibromohexane (II) by means of NaH in THF gives the ether (III), which is condensed with benzylamine (IV) by means of NaI and TEA in DMSO to yield the secondary amine (V). The condensation of (V) with 5-(bromoacetyl)-2-hydroxybenzaldehyde (VI) in refluxing acetonitrile affords the tertiary amine (VII). The reduction of both carbonyl groups of (VII) by means of NaBH4 in methanol affords the dihydroxy amine (VIII), which is finally debenzylated by means of h2 over Pd/C in the same solvent to provide the target salmeterol. The intermediate 5-(bromoacetyl)-2-hydroxybenzaldehyde (VI) has been obtained by Friedel Crafts condensation of 2-hydroxybenzaldehyde (IX) with bromoacetyl chloride (X) by means of AlCl3 in dichloromethane.
| 【1】 Rong, Y.; Ruoho, A.E.; A new synthetic approach to salmeterol. Synth Commun 1999, 29, 12, 2155. |
| 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) | 15147 | Benzylamine; Phenylmethanamine | 100-46-9 | C7H9N | 详情 | 详情 |
| (V) | 35837 | N-benzyl-6-(4-phenylbutoxy)-1-hexanamine; N-benzyl-N-[6-(4-phenylbutoxy)hexyl]amine | C23H33NO | 详情 | 详情 | |
| (VI) | 50873 | 5-(2-bromoacetyl)-2-hydroxybenzaldehyde | C9H7BrO3 | 详情 | 详情 | |
| (VII) | 50874 | 5-(2-[benzyl[6-(4-phenylbutoxy)hexyl]amino]acetyl)-2-hydroxybenzaldehyde | C32H39NO4 | 详情 | 详情 | |
| (VIII) | 35839 | 4-(2-[benzyl[6-(4-phenylbutoxy)hexyl]amino]-1-hydroxyethyl)-2-(hydroxymethyl)phenol | C32H43NO4 | 详情 | 详情 | |
| (IX) | 21351 | 2-Hydroxybenzaldehyde;Salicylic aldehyde；2-Formylphenol;salicylaldehyde | 90-02-8 | C7H6O2 | 详情 | 详情 |
| (X) | 27903 | 2-Bromoacetyl chloride | 22118-09-8 | C2H2BrClO | 详情 | 详情 |