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【结 构 式】 
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【分子编号】37586 【品名】2-fluoroanisole; 1-fluoro-2-methoxybenzene; 2-fluorophenyl methyl ether 【CA登记号】321-28-8 |
【 分 子 式 】C7H7FO 【 分 子 量 】126.1303832 【元素组成】C 66.66% H 5.59% F 15.06% O 12.68% |
合成路线1
该中间体在本合成路线中的序号：(II)This compound can be prepared in two different ways: 1) The condensation of 3-chloro-2-pentanone (I) with 2-fluoroanisole (II) by means of concentrated H2SO4 and subsequent heating at 240 C gives 2,3-bis(3-fluoro-4-methoxyphenyl)-2-pentene (III), which is reduced with H2 over Pd/C in anhydrous AcOH to afford 2,3-bis(3-fluoro-4-methoxyphenyl)pentane (IV). Finally, this compound is demethylated by treatment with refluxing aqueous HBr. 2) The Friedel-Kraft's condensation of (II) with 3-chloro-2-pentanol by means of AlCl3 also gives (IV).
| 【1】 Turner, J.C.; Chan, R.P.-K.; US 4051263 . |
| 【2】 Castaner, J.; Hopkins, S.J.; Bifluranol. Drugs Fut 1981, 6, 9, 531. |
| 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) | 37585 | 3-chloro-2-pentanone | C5H9ClO | 详情 | 详情 | |
| (II) | 37586 | 2-fluoroanisole; 1-fluoro-2-methoxybenzene; 2-fluorophenyl methyl ether | 321-28-8 | C7H7FO | 详情 | 详情 |
| (III) | 37587 | 4-[(E)-1-ethyl-2-(3-fluoro-4-methoxyphenyl)-1-propenyl]-2-fluorophenyl methyl ether; 4-[(E)-1-ethyl-2-(3-fluoro-4-methoxyphenyl)-1-propenyl]-2-fluoro-1-methoxybenzene | C19H20F2O2 | 详情 | 详情 | |
| (IV) | 37588 | 4-[1-ethyl-2-(3-fluoro-4-methoxyphenyl)propyl]-2-fluorophenyl methyl ether; 4-[1-ethyl-2-(3-fluoro-4-methoxyphenyl)propyl]-2-fluoro-1-methoxybenzene | C19H22F2O2 | 详情 | 详情 | |
| (V) | 37589 | 3-chloro-2-pentanol | C5H11ClO | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XXXVII)Nitration of 2-fluoroanisole (XXXVII) with HNO3/Ac2O gives 3-fluoro-4-methoxynitrobenzene (XXXVIII), which is reduced to the corresponding aniline (XXXIX) with SnCl2/HCl. Reaction of compound (XXXIX) with Ac2O yields the acetanilide (XL), which is nitrated with HNO3 to afford 5-fluoro-4-methoxy-2-nitroacetanilide (XLI). Hydrolysis of (XLI) with NaOH provides 5-fluoro-4-methoxy-2-nitroaniline (XLII), which is cyclized with buten-2-one (XXXII) by means of As2O5 and H3PO4 to furnish 5-fluoro-6-methoxy-4-methyl-8-nitroquinoline (XLIII). Condensation of quinoline (XLIII) with 3-(trifluoromethyl)phenol (IV) by means of K2CO3 gives the diaryl ether (XXXIV), which is finally reduced by means of H2 over PtO2 in THF.
| 【1】 McIntyre, J.A.; Castaner, J.; Bayes, M.; Tafenoquine Succinate. Drugs Fut 2003, 28, 9, 859. |
| 【2】 LaMontagne, M.P.; Strube, R.E. (Department of the Army); 4-Methyl-5-(unsubstd. and substd. phenoxy)-6-methoxy-8-(aminoalkylamino)quinolines. US 4431807 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IV) | 33504 | 3-(trifluoromethyl)phenol | 98-17-9 | C7H5F3O | 详情 | 详情 |
| (XIV) | 48075 | 6-methoxy-4-methyl-5-[3-(trifluoromethyl)phenoxy]-8-quinolinylamine; 6-methoxy-4-methyl-5-[3-(trifluoromethyl)phenoxy]-8-quinolinamine | C18H15F3N2O2 | 详情 | 详情 | |
| (XXXII) | 30324 | 3-buten-2-one; methyl vinyl ketone | 78-94-4 | C4H6O | 详情 | 详情 |
| (XXXIV) | 62906 | 6-Methoxy-4-methyl-8-nitro-5-[3-(trifluoromethyl)phenoxy]quinoline; 6-Methoxy-4-methyl-8-nitro-5-quinolinyl 3-(trifluoromethyl)phenyl ether | C18H13F3N2O4 | 详情 | 详情 | |
| (XXXVII) | 37586 | 2-fluoroanisole; 1-fluoro-2-methoxybenzene; 2-fluorophenyl methyl ether | 321-28-8 | C7H7FO | 详情 | 详情 |
| (XXXVIII) | 62907 | 2-Fluoro-4-nitrophenyl methyl ether; 2-Fluoro-1-methoxy-4-nitrobenzene | 455-93-6 | C7H6FNO3 | 详情 | 详情 |
| (XXXIX) | 20483 | 3-fluoro-4-methoxyphenylamine; 3-fluoro-4-methoxyaniline | 366-99-4 | C7H8FNO | 详情 | 详情 |
| (XL) | 62908 | N-(3-Fluoro-4-methoxyphenyl)acetamide | C9H10FNO2 | 详情 | 详情 | |
| (XLI) | 62909 | N-(5-Fluoro-4-methoxy-2-nitrophenyl)acetamide | C9H9FN2O4 | 详情 | 详情 | |
| (XLII) | 62910 | 5-Fluoro-4-methoxy-2-nitrophenylamine; 5-Fluoro-4-methoxy-2-nitroaniline | C7H7FN2O3 | 详情 | 详情 | |
| (XLIII) | 62911 | 5-Fluoro-4-methyl-8-nitro-6-quinolinyl methyl ether; 5-Fluoro-6-methoxy-4-methyl-8-nitroquinoline | C11H9FN2O3 | 详情 | 详情 |