4-ethyl-5-fluoro-2-methoxyphenol

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Potassium hydroxide (2.4 g, 43.13 mmol) was added to a solution of 4-ethyl-5-fluoro-2-methoxyphenol (6.1 g, 35.94 mmol) and 3,4-difluorobenzonitrile (5.0 g, 35.94 mmol) in anhydrous acetonitrile (80 mL). The reaction mixture was stirred at 85° C. overnight then concentrated under vacuum. The residue was solubilized in ethyl acetate (300 mL) and diluted by addition of a saturated solution of ammonium chloride (200 mL). The aqueous layer was separated and extracted with ethyl acetate (2×200 mL). The combined organic phases were dried over sodium sulfate, filtered and concentrated to dryness to give a brown solid. After trituration in pentane, the title product was obtained as a brown solid (8.10 g, 77%). then concentrated under vacuum diluted by addition of a saturated solution of ammonium chloride (200 mL) The aqueous layer was separated extracted with ethyl acetate (2×200 mL) The combined organic phases were dried over sodium sulfate filtered concentrated to dryness to give a brown solid

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of 4-ethyl-5-fluoro-2-methoxyphenol (1 g, 5.87 mmol), 3,4-difluorobenzonitrile (899 mg, 6.46 mmol) and potassium hydroxide (395 mg, 7.04 mmol) in anhydrous acetonitrile (35 mL) under argon was stirred at 80° C. overnight. The reaction mixture was concentrated under vacuum and diluted with ethyl acetate and a saturated aqueous solution of ammonium chloride. The aqueous layer was separated and extracted twice with ethyl acetate. The combined organic phases were dried over sodium sulfate, filtrated and concentrated in vacuo to give a brown oil (1.6 g). The crude product was purified by flash chromatography on silica gel, using cyclohexane/ethyl acetate (9:1) as eluent. The title product was obtained as a colourless oil that crystallized slowly (1.42 g, 84%). The reaction mixture was concentrated under vacuum diluted with ethyl acetate The aqueous layer was separated extracted twice with ethyl acetate The combined organic phases were dried over sodium sulfate filtrated concentrated in vacuo

Conditions: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Potassium hydroxide (2.4 g, 43.13 mmol) was added to a solution of 4-ethyl-5-fluoro-2-methoxyphenol (6.1 g, 35.94 mmol) and 3,4-difluorobenzonitrile (5.0 g, 35.94 mmol) in anhydrous acetonitrile (80 mL). The reaction mixture was stirred at 85° C. overnight then concentrated under vacuum. The residue was solubilized in ethyl acetate (300 mL) and diluted by addition of a saturated solution of ammonium chloride (200 mL). The aqueous layer was separated and extracted with ethyl acetate (2×200 mL). The combined organic phases were dried over sodium sulfate, filtered and concentrated to dryness to give a brown solid. After trituration in pentane, the title product was obtained as a brown solid (8.10 g, 77%). then concentrated under vacuum diluted by addition of a saturated solution of ammonium chloride (200 mL) The aqueous layer was separated extracted with ethyl acetate (2×200 mL) The combined organic phases were dried over sodium sulfate filtered concentrated to dryness to give a brown solid

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of 4-ethyl-5-fluoro-2-methoxyphenol (1 g, 5.87 mmol), 3,4-difluorobenzonitrile (899 mg, 6.46 mmol) and potassium hydroxide (395 mg, 7.04 mmol) in anhydrous acetonitrile (35 mL) under argon was stirred at 80° C. overnight. The reaction mixture was concentrated under vacuum and diluted with ethyl acetate and a saturated aqueous solution of ammonium chloride. The aqueous layer was separated and extracted twice with ethyl acetate. The combined organic phases were dried over sodium sulfate, filtrated and concentrated in vacuo to give a brown oil (1.6 g). The crude product was purified by flash chromatography on silica gel, using cyclohexane/ethyl acetate (9:1) as eluent. The title product was obtained as a colourless oil that crystallized slowly (1.42 g, 84%). The reaction mixture was concentrated under vacuum diluted with ethyl acetate The aqueous layer was separated extracted twice with ethyl acetate The combined organic phases were dried over sodium sulfate filtrated concentrated in vacuo

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of 4-ethyl-5-fluoro-2-methoxyphenol (1 g, 5.87 mmol), 3,4-difluorobenzonitrile (899 mg, 6.46 mmol) and potassium hydroxide (395 mg, 7.04 mmol) in anhydrous acetonitrile (35 mL) under argon was stirred at 80° C. overnight. The reaction mixture was concentrated under vacuum and diluted with ethyl acetate and a saturated aqueous solution of ammonium chloride. The aqueous layer was separated and extracted twice with ethyl acetate. The combined organic phases were dried over sodium sulfate, filtrated and concentrated in vacuo to give a brown oil (1.6 g). The crude product was purified by flash chromatography on silica gel, using cyclohexane/ethyl acetate (9:1) as eluent. The title product was obtained as a colourless oil that crystallized slowly (1.42 g, 84%). The reaction mixture was concentrated under vacuum diluted with ethyl acetate The aqueous layer was separated extracted twice with ethyl acetate The combined organic phases were dried over sodium sulfate filtrated concentrated in vacuo

Conditions: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Potassium hydroxide (2.4 g, 43.13 mmol) was added to a solution of 4-ethyl-5-fluoro-2-methoxyphenol (6.1 g, 35.94 mmol) and 3,4-difluorobenzonitrile (5.0 g, 35.94 mmol) in anhydrous acetonitrile (80 mL). The reaction mixture was stirred at 85° C. overnight then concentrated under vacuum. The residue was solubilized in ethyl acetate (300 mL) and diluted by addition of a saturated solution of ammonium chloride (200 mL). The aqueous layer was separated and extracted with ethyl acetate (2×200 mL). The combined organic phases were dried over sodium sulfate, filtered and concentrated to dryness to give a brown solid. After trituration in pentane, the title product was obtained as a brown solid (8.10 g, 77%). then concentrated under vacuum diluted by addition of a saturated solution of ammonium chloride (200 mL) The aqueous layer was separated extracted with ethyl acetate (2×200 mL) The combined organic phases were dried over sodium sulfate filtered concentrated to dryness to give a brown solid

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of 4-ethyl-5-fluoro-2-methoxyphenol (1 g, 5.87 mmol), 3,4-difluorobenzonitrile (899 mg, 6.46 mmol) and potassium hydroxide (395 mg, 7.04 mmol) in anhydrous acetonitrile (35 mL) under argon was stirred at 80° C. overnight. The reaction mixture was concentrated under vacuum and diluted with ethyl acetate and a saturated aqueous solution of ammonium chloride. The aqueous layer was separated and extracted twice with ethyl acetate. The combined organic phases were dried over sodium sulfate, filtrated and concentrated in vacuo to give a brown oil (1.6 g). The crude product was purified by flash chromatography on silica gel, using cyclohexane/ethyl acetate (9:1) as eluent. The title product was obtained as a colourless oil that crystallized slowly (1.42 g, 84%). The reaction mixture was concentrated under vacuum diluted with ethyl acetate The aqueous layer was separated extracted twice with ethyl acetate The combined organic phases were dried over sodium sulfate filtrated concentrated in vacuo

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of 4-ethyl-5-fluoro-2-methoxyphenol (1 g, 5.87 mmol), 3,4-difluorobenzonitrile (899 mg, 6.46 mmol) and potassium hydroxide (395 mg, 7.04 mmol) in anhydrous acetonitrile (35 mL) under argon was stirred at 80° C. overnight. The reaction mixture was concentrated under vacuum and diluted with ethyl acetate and a saturated aqueous solution of ammonium chloride. The aqueous layer was separated and extracted twice with ethyl acetate. The combined organic phases were dried over sodium sulfate, filtrated and concentrated in vacuo to give a brown oil (1.6 g). The crude product was purified by flash chromatography on silica gel, using cyclohexane/ethyl acetate (9:1) as eluent. The title product was obtained as a colourless oil that crystallized slowly (1.42 g, 84%). The reaction mixture was concentrated under vacuum diluted with ethyl acetate The aqueous layer was separated extracted twice with ethyl acetate The combined organic phases were dried over sodium sulfate filtrated concentrated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir: