5-(2-Fluorophenyl)-1H-pyrrole-3-carbaldehyde

1240948-77-9

881674-56-2

5-(2-Fluorophenyl)-1H-pyrrole-3-carbonitrile (5.0 g, 26.9 mmol) was added to a four-necked flask with THF (33 mL) and stirred at 15-25 °C until completely dissolved. Subsequently, acetic acid (55 mL) and water (11 mL) were added sequentially. Under nitrogen protection, Raney nickel catalyst (Kawaken Fine Chemicals Co., Ltd., NDHT-90, 2.5 mL, wet weight 4 g) was added. The reaction mixture was stirred vigorously at 15-25 °C for about 3 h under hydrogen atmosphere. Upon completion of the reaction, the hydrogen was replaced with nitrogen, the Raney nickel was removed by filtration, and the catalyst was washed with ethyl acetate (50 mL). The filtrate was adjusted to pH 7 with 5N aqueous sodium hydroxide (~180 mL) at 10-35 °C. The organic layer was washed sequentially with 5% aqueous sodium bicarbonate (25 mL) and 5% brine (25 mL). Water (25 mL) was added to the organic layer and washed again with water. Subsequently, the pH was adjusted to 3.0-3.5 with 6N hydrochloric acid at 15-25 °C. After stirring overnight, the organic layer was separated and washed with 5% brine (25 mL). The organic layer was concentrated under reduced pressure, warmed to 65-70 °C and then cooled to 45-55 °C with continued stirring for 1 hour. Further cooled to 15 °C, n-heptane (25 mL) was added dropwise and stirred at the same temperature for 1 hour. Finally, the mixture was stirred at 0-10 °C for 1 h. The precipitated crystals were collected by filtration, washed with ethyl acetate:n-heptane (1:2, 15 mL), and dried under reduced pressure at 50 °C to constant weight to afford the target product 5-(2-fluorophenyl)-1H-pyrrole-3-carbaldehyde (23.9 g, 78% yield). The product was confirmed by 1H-NMR (300 MHz, DMSO-d6) and elemental analysis with melting point 123.0-126.0 °C.