2-cyano-N-(4-fluorophenyl)acetamide

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-cyano-N-(4-fluorophenyl)acetamide (1.7 g, 10.6 mmol) in dimethyleneglycol monomethylether (20 mL) were added 1,4-diazabicyclo[2.2.2]octane (1.2 g, 10.6 mmol) and (1E)-1-methoxypent-1-en-3-one (1.82 g, 15.9 mmol), and the mixture was stirred at 120° C. for 12 hr. The reaction mixture was diluted with 1N hydrochloric acid and ethyl acetate, and extracted 3 times with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and filtered. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (NH silica gel, ethyl acetate/hexane=50/50→100/0) to give a white solid. The white solid was washed with ethyl acetate to give the title compound (410 mg, 16%) as a white solid. extracted 3 times with ethyl acetate The organic layer was washed with saturated brine dried over anhydrous magnesium sulfate filtered The solvent was evaporated under reduced pressure The obtained residue was purified by silica gel column chromatography (NH silica gel, ethyl acetate/hexane=50/50→100/0) to give a white solid The white solid was washed with ethyl acetate

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-cyano-N-(4-fluorophenyl)acetamide (2 g, 11.2 mmol) and (3E)-4-ethoxy-1,1,1-trifluorobut-3-en-2-one (2.26 g, 13.4 mmol) in dimethyleneglycol monomethylether (20 mL) was added 1,4-diazabicyclo[2.2.2]octane (1.26 g, 11.2 mmol), and the mixture was stirred at 120° C. for 6 hr. The reaction mixture was diluted with 1N hydrochloric acid and ethyl acetate, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and filtered. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (NH silica gel, ethyl acetate/hexane=1/2→1/1) to give a white solid. The white solid was washed with ethyl acetate and collected by filtration to give the title compound (230 mg, 7.2%) as a white solid. the mixture was extracted 3 times with ethyl acetate The organic layer was washed with saturated brine dried over anhydrous magnesium sulfate filtered The solvent was evaporated under reduced pressure The obtained residue was purified by silica gel column chromatography (NH silica gel, ethyl acetate/hexane=1/2→1/1) to give a white solid The white solid was washed with ethyl acetate collected by filtration

Conditions: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of (1E)-1-methoxy-4-methylpenta-1-en-3-one (508 mg, 3.96 mmol), 2-cyano-N-(4-fluorophenyl)acetamide (847 mg, 4.75 mmol), 1,4-diazabicyclo[2.2.2]octane (444 mg, 3.96 mmol) and 2-(2-methoxyethoxy)ethanol (10 mL) was stirred at 130° C. for 6 hr. After cooling to room temperature, the mixture was diluted with ethyl acetate, washed with 1N hydrochloric acid, water (×2) and saturated brine, dried over anhydrous magnesium sulfate and filtered. The solvent was evaporated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane=0/100→60/40) and silica gel column chromatography (NH silica gel, ethyl acetate/hexane=0/100→60/40) to give the title compound (604 mg, 59%) as a yellow solid. After cooling to room temperature washed with 1N hydrochloric acid, water (×2) and saturated brine dried over anhydrous magnesium sulfate filtered The solvent was evaporated under reduced pressure the obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane=0/100→60/40) and silica gel column chromatography (NH silica gel, ethyl acetate/hexane=0/100→60/40)

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 2-cyano-N-(4-fluorophenyl)acetamide (15 g, 84.2 mmol), 4-methoxybut-3-en-2-one (12.6 g, 125.9 mmol) and 1,4-diazabicyclo[2.2.2]octane (9.4 g, 84.2 mmol) in 2-(2-methoxyethoxy)ethanol (150 mL) was stirred with heating at 120° C. for 5 hr. (3E)-4-Methoxybut-3-en-2-one (4.2 g, 41.9 mmol) and 1,4-diazabicyclo[2,2,2]octane (4.7 g, 41.9 mmol) were further added to the reaction mixture, and the mixture was stirred with heating at 120° C. for 1 hr. 2N Hydrochloric acid was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and filtered, and the solvent was evaporated under reduced pressure. The obtained solid was washed with ethyl acetate to give the title compound (6 g, 31%) as a pale-brown solid. with heating at 120° C. for 1 hr the mixture was extracted with ethyl acetate The organic layer was washed with saturated brine dried over anhydrous magnesium sulfate filtered the solvent was evaporated under reduced pressure The obtained solid was washed with ethyl acetate