反应详情

A solution of sodium nitrite (36 g, 0.51 mole) in water (50 mL) was slowly added to a solution of 5-fluoro-2-methoxy-phenylamine (61.5 g, 0.48 mol) in hydrochloric acid (20% aqueous solution, 115 mL) at 0° C. After stirring for 10 minutes, a cooled (0° C.) solution of acrolein (50 mL, 0.75 mol) in acetone (100 mL) containing calcium oxide (0.56 g, 0.010 mol) was added slowly to the reaction mixture. This was then followed by a solution of cuprous chloride (5 g, 0.05 mol) in acetone (100 mL) containing hydrochloric acid (20% aqueous solution, 10 mL). The mixture was stirred at 0 to 30° C. for 3 hours, and then extracted three times with dichloromethane (300 mL). The combined organic layers were washed with a saturated aqueous solution of sodium bicarbonate, a saturated aqueous solution of sodium chloride, dried over sodium sulfate, filtered, and evaporated to dryness to give a black viscous oil. The crude product was passed through a short silica column to give the crude product, which was used directly in the next step.

1. additionwas added slowly to the reaction mixture
2. stirringThe mixture was stirred at 0 to 30° C. for 3 hours
3. extractionextracted three times with dichloromethane (300 mL)
4. washThe combined organic layers were washed with a saturated aqueous solution of sodium bicarbonate
5. dry with materiala saturated aqueous solution of sodium chloride, dried over sodium sulfate
6. filtrationfiltered
7. customevaporated to dryness
8. customto give a black viscous oil