3-(3-fluorophenyl)prop-2-enenitrile

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 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. is added dropwise The reaction product is then extracted with ethyl acetate the organic phase is dried over sodium sulfate the solvent is evaporated off under reduced pressure to give a brown solid, which purified by chromatography on a column of 600 g of silica gel eluting with dichloromethane with a mixture of 1% methanol in dichloromethane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 35.0 g (411 mmol) of cyanoacetic acid (CAS 372-09-8) and 56.2 g (453 mmol) of 3-fluorobenzaldehyde (CAS 456-48-4) in a mixture of 400 ml of toluene and 220 ml of pyridine is refluxed for 22 hours using Dean-Stark apparatus to remove the water formed during the reaction. The solvent is then removed under reduced pressure and the residue is co-evaporated 3 times with toluene. The residue is then taken up in ethyl acetate and the organic phase is washed successively with aqueous 1N sodium hydroxide solution, aqueous 1N hydrochloric acid solution and then with saturated sodium chloride solution. The organic phase is then dried over sodium sulfate and the solvent is evaporated off under reduced pressure to give a brown oil, which is chromatographed on a column of silica gel, eluting with toluene, to give 48.5 g a mixture of (E) and (Z) 3-(3-fluorophenyl)-2-propenenitrile in a ratio of (7/3) is refluxed for 22 hours to remove the water formed during the reaction The solvent is then removed under reduced pressure the organic phase is washed successively with aqueous 1N sodium hydroxide solution, aqueous 1N hydrochloric acid solution The organic phase is then dried over sodium sulfate the solvent is evaporated off under reduced pressure to give a brown oil, which is chromatographed on a column of silica gel eluting with toluene

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 35.0 g (411 mmol) of cyanoacetic acid (CAS 372-09-8) and 56.2 g (453 mmol) of 3-fluorobenzaldehyde (CAS 456-48-4) in a mixture of 400 ml of toluene and 220 ml of pyridine is refluxed for 22 hours using Dean-Stark apparatus to remove the water formed during the reaction. The solvent is then removed under reduced pressure and the residue is co-evaporated 3 times with toluene. The residue is then taken up in ethyl acetate and the organic phase is washed successively with aqueous 1N sodium hydroxide solution, aqueous 1N hydrochloric acid solution and then with saturated sodium chloride solution. The organic phase is then dried over sodium sulfate and the solvent is evaporated off under reduced pressure to give a brown oil, which is chromatographed on a column of silica gel, eluting with toluene, to give 48.5 g a mixture of (E) and (Z) 3-(3-fluorophenyl)-2-propenenitrile in a ratio of (7/3) is refluxed for 22 hours to remove the water formed during the reaction The solvent is then removed under reduced pressure the organic phase is washed successively with aqueous 1N sodium hydroxide solution, aqueous 1N hydrochloric acid solution The organic phase is then dried over sodium sulfate the solvent is evaporated off under reduced pressure to give a brown oil, which is chromatographed on a column of silica gel eluting with toluene

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 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. is added dropwise The reaction product is then extracted with ethyl acetate the organic phase is dried over sodium sulfate the solvent is evaporated off under reduced pressure to give a brown solid, which purified by chromatography on a column of 600 g of silica gel eluting with dichloromethane with a mixture of 1% methanol in dichloromethane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 35.0 g (411 mmol) of cyanoacetic acid (CAS 372-09-8) and 56.2 g (453 mmol) of 3-fluorobenzaldehyde (CAS 456-48-4) in a mixture of 400 ml of toluene and 220 ml of pyridine is refluxed for 22 hours using Dean-Stark apparatus to remove the water formed during the reaction. The solvent is then removed under reduced pressure and the residue is co-evaporated 3 times with toluene. The residue is then taken up in ethyl acetate and the organic phase is washed successively with aqueous 1N sodium hydroxide solution, aqueous 1N hydrochloric acid solution and then with saturated sodium chloride solution. The organic phase is then dried over sodium sulfate and the solvent is evaporated off under reduced pressure to give a brown oil, which is chromatographed on a column of silica gel, eluting with toluene, to give 48.5 g a mixture of (E) and (Z) 3-(3-fluorophenyl)-2-propenenitrile in a ratio of (7/3) is refluxed for 22 hours to remove the water formed during the reaction The solvent is then removed under reduced pressure the organic phase is washed successively with aqueous 1N sodium hydroxide solution, aqueous 1N hydrochloric acid solution The organic phase is then dried over sodium sulfate the solvent is evaporated off under reduced pressure to give a brown oil, which is chromatographed on a column of silica gel eluting with toluene

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 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. is added dropwise The reaction product is then extracted with ethyl acetate the organic phase is dried over sodium sulfate the solvent is evaporated off under reduced pressure to give a brown solid, which purified by chromatography on a column of 600 g of silica gel eluting with dichloromethane with a mixture of 1% methanol in dichloromethane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 35.0 g (411 mmol) of cyanoacetic acid (CAS 372-09-8) and 56.2 g (453 mmol) of 3-fluorobenzaldehyde (CAS 456-48-4) in a mixture of 400 ml of toluene and 220 ml of pyridine is refluxed for 22 hours using Dean-Stark apparatus to remove the water formed during the reaction. The solvent is then removed under reduced pressure and the residue is co-evaporated 3 times with toluene. The residue is then taken up in ethyl acetate and the organic phase is washed successively with aqueous 1N sodium hydroxide solution, aqueous 1N hydrochloric acid solution and then with saturated sodium chloride solution. The organic phase is then dried over sodium sulfate and the solvent is evaporated off under reduced pressure to give a brown oil, which is chromatographed on a column of silica gel, eluting with toluene, to give 48.5 g a mixture of (E) and (Z) 3-(3-fluorophenyl)-2-propenenitrile in a ratio of (7/3) is refluxed for 22 hours to remove the water formed during the reaction The solvent is then removed under reduced pressure the organic phase is washed successively with aqueous 1N sodium hydroxide solution, aqueous 1N hydrochloric acid solution The organic phase is then dried over sodium sulfate the solvent is evaporated off under reduced pressure to give a brown oil, which is chromatographed on a column of silica gel eluting with toluene