In a 100 mL-volume glass flask equipped with a stirrer, a thermometer and a dropping funnel were placed under argon atmosphere 4.98 g (17.1 mmol) of 2-cyclo-propyl-4-(4-fluorophenyl)quinoline-3-carbaldehyde, 3.10 mL (18.8 mmol) of diethylcyanomethyl phosphonate (purity 98%), 0.15 mL (0.33 mmol) of tricaprilmethylammonium chloride (Aliquat 336, available from Aldrich Corp.), and 35 mL of toluene. To the content kept at 25-35° C. (liquid temperature) was slowly added 10.1 g (50.5 mmol) of aqueous sodium hydroxide solution (20 wt. %), and the mixture was reacted for 3 hours at the same temperature. Subsequently, 0.14 mL (0.85 mmol) of diethyl (cyanomethyl)-phosphonate (purity 98%) was added, and the mixture was reacted for 66 hours at the same temperature. After the reaction was complete, 5 mL of water was added to the reaction mixture, and the mixture was stirred for 30 minutes. To the mixture was added 50 mL of toluene, and the organic portion is taken out. The organic portion was washed with 10 mL of an aqueous sodium hydroxide solution (10 wt. %), and to the washed portion was added 10 mL of saturated aqueous sodium chloride solution. The aqueous mixture was neutralized by addition of 5.6 mL of hydrochloric acid (1 mol/L)., and the organic portion was taken out. The organic portion was placed in a 200 mL-volume glass flask equipped with a stirrer. To the organic portion was added 1.60 g of anhydrous sodium sulfate, and the mixture was stirred for one hour at room temperature. To the mixture were further added 0.14 g of active carbon (powder, available from Wako Junyaku Co., Ltd.) and 0.62 g of silica gel (Wakogel C-200, available from Wako Junyaku Co., Ltd.). The mixture was then stirred for 1.75 hours at room temperature, and filtered. through a celite. The celite was washed with 50 mL of toluene. The reaction liquid was concentrated under reduced pressure to precipitate a crystalline product. The crystalline product was heated to melt, and after addition of 30 mL of hexane, heated under reflux for 30 minutes. Thereafter, the liquid was chilled to 5° C., and stirred for 2 hours to precipitate a crystalline product. The crystalline product was collected by filtration, washed with 30 mL of hexane, and dried at 55° C. under reduced pressure, to obtain 4.81 g (yield 90%) of 3-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl]prop-2-enenitrile as a white crystalline product.
