Propargyl bromide → 3-(2-Methyl-1H-imidazo[4,5-c]quinolin-1-yl)propyl (Prop-2-ynyl) Ether

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Reaction Steps

To 3-(2-methyl-1H-imidazo[4,5-c]quinolin-1-yl)-1-propanol (12.2 g, 50.56 mmol) dissolved in dichloromethane (180 mL) was added sodium hydroxide (180 mL of 50%) with mechanical stirring. Benzyltrimethylammonium chloride (1.88 g, 10.11 mmol) was added to the resulting suspension, and after stirring for 5 minutes, propargyl bromide (17 mL of 80% in toluene, 141.8 mmol) was added. The resulting reaction mixture was allowed to stir at ambient temperature. After 2 hours, TLC monitoring indicated 50% completion, and after 4.5 hours HPLC monitoring indicated 20% starting material remaining. More propargyl bromide (5 mL of 80% in toluene, 40.51 mmol) was added, and the resulting reaction mixture was allowed to stir at ambient temperature for 64.5 hours. The layers were separated, and the organic layer was washed with water (3×) and brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting dark oil was dissolved in dichloromethane and again extracted with water, dried over sodium sulfate, and concentrated under reduced pressure. The resulting dark oil was purified by silica gel column chromatography using 98/2 dichloromethane/methanol as the eluant. After removing the solvent from the collected fractions, 5.880 g of pure (by HNMR analysis) product was obtained. This material was recrystallized from ethyl acetate/hexane to provide 4.658 g of brown crystals.

Provenance & Evidence