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With caesium carbonate; In tetrahydrofuran; 1,4-dioxane; at 20 - 90℃; |
Step 3. To a 1 :1 THF-1 ,4-dioxane solution of <strong>[590371-90-7]4-chloro-3-iodo-quinoline</strong> (459 mg, 1.59 mmol) was added 2-methyl-3-tetrahydrofuranthiol (225 mg, 1.90 mmol), followed by cesium carbonate (1.55 g, 4.77 mol). The reaction mixture was heated at 90 0C for 4h, then at ambient temperature overnight. TLC analysis (4:1 hexanes-ethyl acetate) shows a complete consumption of the starting material. The reaction was diluted with EtOAc and water. The phases were separated, and the aqueous was extracted 2 times with EtOAc. The combined organics were dried over sodium sulfate and filtered, and the solvent was evaporated. The crude material was purified using silica gelchromatography eluting with 9:1 hexanes-EtOAc then 4:1 hexanes-EtOAc, yielding 300 mg of pure 3-iodo-4-(2-methyl-tetrahydro-furan-3-ylsulfanyl)-quinoline. An additional purification of the impure fractions yielded an additional 150 mg of pure material. LCMS: m/z 373 (M+2)+ and 1H NMR (CDCI3, 400 MHz): delta 9.23 (s, 1 H), 8.62 (d, 1 H), 8.1 1 (d, 1 H), 7.78 (t, 1 H), 7.64 (t, 1 H), 3.97-3.90 (m, 3H), 3.48-3.39 (m, 1 H), 2.31-2.19 (m, 1 H), 2.02-1.94 (m, 1 H), 1.11 (d, 3H). |
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With caesium carbonate; In tetrahydrofuran; 1,4-dioxane; at 20 - 90℃; for 4h; |
3-Iodo-4-(2-methyl-tetrahydro-furan-3-ylsulfanyl)-quinoline may be prepared from <strong>[590371-90-7]4-chloro-3-iodo-quinoline</strong> using the following procedure. To a 1:1 THF-1,4-dioxane solution of <strong>[590371-90-7]4-chloro-3-iodo-quinoline</strong> may be added 2-methyl-3-tetrahydrofuranthiol, followed by cesium carbonate. The reaction mixture may be heated at 90 C. for 4 hours, then at ambient temperature overnight until thin layer chromatography analysis (4:1 hexanes-ethyl acetate eluent) shows a complete consumption of the starting material. The reaction may then be diluted with ethyl acetate and water, the phases separated, and the aqueous extracted 2 times with ethyl acetate. The combined organics may be dried over sodium sulfate, filtered, and the solvent evaporated. The crude material was purified using silica gel chromatography eluting with 9:1 hexanes-EtOAc to provide 4:1 hexanes-ethyl acetate 3-iodo-4-(2-methyl-tetrahydro-furan-3-ylsulfanyl)-quinoline. |