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【结 构 式】 
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【分子编号】12947 【品名】1-(1-Benzothiophen-2-yl)-1-ethanone 【CA登记号】22720-75-8 |
【 分 子 式 】C10H8OS 【 分 子 量 】176.23892 【元素组成】C 68.15% H 4.58% O 9.08% S 18.19% |
合成路线1
该中间体在本合成路线中的序号：(I)The synthesis of zileuton involved conventional synthetic procedures starting with 2-acetylbenzo[b]thiophene. Treatment of a solution of 2-acetylbenzo[b]thiophene (I) in ethanol/pyridine (1:1) with hydroxylamine hydrochloride at room temperature provided the corresponding oxime (II). To the oxime (II) dissolved in ethanol was added borane:pyridine complex followed by the dropwise addition of 20% HCl in ethanol to provide the hydroxylamine (III), isolated by extraction after neutralization of the acidic mixture. The hydroxylamine (III) was converted to zileuton by either heating with trimethylsilylisocyanate in dioxane or by reacting with KOCN and aqueous HCl.
| 【1】 Summers, J.B. Jr.; Gunn, B.P.; Brooks, D.W. (Abbott Laboratories Inc.); Indole, benzofuran, benzothiophene containing lipoxygenease inhibiting compounds. EP 0279263; JP 1988264456; US 4873259 . |
| 【2】 Brooks, D.W.; Rubin, P.D.; Carter, G.W.; Dube, L.M.; Bell, R.L.; Zileuton. Drugs Fut 1993, 18, 7, 616. |
合成路线2
该中间体在本合成路线中的序号：(I)A new efficient synthesis of 2-acetylbenzothiophene (I), the key starting material for the previously reported synthesis of zileuton, has been described: Thiophenol (II) is dilithiated with butyllithium and tetramethylethylenediamine in cyclohexane to compound (III), which is then cyclized by successive treatments with DMF and chloroacetone (IV) in THF to afford (I) in high yield.
| 【1】 Brooks, D.W.; Basha, A.; Synthesis of the 5-lipoxygenase inhibitor zileuton from thiophenol. J Org Chem 1993, 58, 5, 1293. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 15288 | 1-Chloroacetone; Chloroacetone | 78-95-5 | C3H5ClO | 详情 | 详情 | |
| (I) | 12947 | 1-(1-Benzothiophen-2-yl)-1-ethanone | 22720-75-8 | C10H8OS | 详情 | 详情 |
| (II) | 12951 | Benzenethiol; Phenylmercaptan; Phenylhydrosulfide | 108-98-5 | C6H6S | 详情 | 详情 |
| (III) | 12952 | 2-Lithio-thiophenol lithium salt | C6H4Li2S | 详情 | 详情 |