Tetrahydrofuran → 4-(3-Fluorophenyl)-1H-pyrrole-3-carbonitrile

Participants

Reaction Conditions

Reaction Steps

To a suspension of 19.8 g (494 mmol) of sodium hydride at 60% in oil in 350 ml of anhydrous tetrahydrofuran is added dropwise a mixture of 48.5 g (330 mmol) of the mixture of (Z) and (E) 3-(3-fluorophenyl)-2-propenenitrile in a ratio of (7/3) and 64.4 g (330 mmol) of tosylmethyl isocyanide (CAS 36635-61-7) dissolved in 250 ml of tetrahydrofuran, while maintaining the temperature of the reaction medium at about 25° C. The mixture is then stirred for 1 hour at room temperature and is then poured into ice-water. The reaction product is then extracted with ethyl acetate, the organic phase is dried over sodium sulfate and the solvent is evaporated off under reduced pressure to give a brown solid, which is dissolved in 350 ml of hot chloroform and purified by chromatography on a column of 600 g of silica gel, eluting with dichloromethane and then with a mixture of 1% methanol in dichloromethane, to give 41.5 g of 4-(3-fluorophenyl)-1H-pyrrole-3-carbonitrile in the form of a beige-coloured solid after triturating in dichloromethane, filtering off and drying.

Provenance & Evidence