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【结 构 式】 
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【分子编号】16210 【品名】4-(benzyloxy)-2-(3-chloropropoxy)-1-ethylbenzene; benzyl 3-(3-chloropropoxy)-4-ethylphenyl ether 【CA登记号】 |
【 分 子 式 】C18H21ClO2 【 分 子 量 】304.81624 【元素组成】C 70.93% H 6.94% Cl 11.63% O 10.5% |
合成路线1
该中间体在本合成路线中的序号：(III)The biphenyl side chain of LY293111 can be constructed as illustrated in Scheme 19757001a: 4-Benzyloxy-2-hydroxyacetophenone (I) is alkylated with 1-bromo-3-chloropropane to provide compound (II). Reduction of the keto group with triethylsilane in trifluoroacetic acid provides (III), which is then regiospecifically brominated with N-bromosuccinimide to give (IV). A Suzuki biaryl coupling of (IV) with 4-fluorophenylboronic acid is used to prepare chloride (V), which is treated with sodium iodide in refluxing 2-butanone to give intermediate iodide (VI).
| 【1】 Schmittling, E.A.; Sawyer, J.S.; Synthesis of diaryl ethers, diaryl thioethers, and diaryl amines mediated by potassium fluoride-alumina and 18-crown-6. J Org Chem 1993, 58, 3229-30. |
| 【2】 Sawyer, J.S.; Bach, N.J.; Baker, S.R.; et al.; Synthetic and structure/activity studies on acid-substituted 2-arylphenols: The discovery of 2-[2-propyl-3-[3-[2-ethyl-4-(4-fluorophenyl)-5-hydroxyphenoxy]propoxy]phenoxy]benzoic acid, a high-affinity leukotriene B4 receptor antagonist. J Med Chem 1995, 38, 22, 4411-32. |
| 【3】 Sawyer, J.S.; Baldwin, R.F.; Sofia, M.J.; et al.; Biphenylyl-substituted xanthones: Highly potent leukotriene B4 receptor antagonists. J Med Chem 1993, 36, 24, 3982-4. |
| 【4】 Sawyer, J.S.; LY-293111 Sodium. Drugs Fut 1996, 21, 6, 610. |
| 【5】 Sawyer, J.S.; Baldwin, R.F.; Saussy, D.L. Jr.; Froelich, L.L.; Jackson, W.T.; Diaryl ether/carboxylic acid derivatives of LY255283: Receptor antagonists of leukotriene B4. Bioorg Med Chem Lett 1993, 3, 10, 1985-90. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 10358 | 1-Bromo-3-chloropropane | 109-70-6 | C3H6BrCl | 详情 | 详情 | |
| 38403 | 4-fluorophenylboronic acid | 1765-93-1 | C6H6BFO2 | 详情 | 详情 | |
| (I) | 16208 | 4'-Benzyloxy-2'-hydroxyacetophenone; 1-[4-(Benzyloxy)-2-hydroxyphenyl]-1-ethanone | 29682-12-0 | C15H14O3 | 详情 | 详情 |
| (II) | 16209 | 1-[4-(benzyloxy)-2-(3-chloropropoxy)phenyl]-1-ethanone | C18H19ClO3 | 详情 | 详情 | |
| (III) | 16210 | 4-(benzyloxy)-2-(3-chloropropoxy)-1-ethylbenzene; benzyl 3-(3-chloropropoxy)-4-ethylphenyl ether | C18H21ClO2 | 详情 | 详情 | |
| (IV) | 16211 | benzyl 2-bromo-5-(3-chloropropoxy)-4-ethylphenyl ether; 1-(benzyloxy)-2-bromo-5-(3-chloropropoxy)-4-ethylbenzene | C18H20BrClO2 | 详情 | 详情 | |
| (V) | 16212 | benzyl 4-(3-chloropropoxy)-5-ethyl-4'-fluoro[1,1'-biphenyl]-2-yl ether; 2-(benzyloxy)-4-(3-chloropropoxy)-5-ethyl-4'-fluoro-1,1'-biphenyl | C24H24ClFO2 | 详情 | 详情 | |
| (VI) | 16213 | benzyl 5-ethyl-4'-fluoro-4-(3-iodopropoxy)[1,1'-biphenyl]-2-yl ether; 2-(benzyloxy)-5-ethyl-4'-fluoro-4-(3-iodopropoxy)-1,1'-biphenyl | C24H24FIO2 | 详情 | 详情 |