N([O-])=O.[Na+].[F:5][C:6]1[CH:7]=[CH:8][C:9]([O:13][CH3:14])=[C:10](N)[CH:11]=1.[CH:15]([CH:17]=[CH2:18])=[O:16].[O-2].[Ca+2].[ClH:21]>O.CC(C)=O>[Cl:21][CH:17]([CH2:18][C:10]1[CH:11]=[C:6]([F:5])[CH:7]=[CH:8][C:9]=1[O:13][CH3:14])[CH:15]=[O:16]
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.
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