1,1,1-Trifluoro-4-methylpent-3-en-2-one → 1,1,1-Trifluoro-4-(5-fluoro-2-methylphenyl)-4-methylpentan-2-one

Participants

Reaction Steps

To a slurry of 1,1,1-trifluoro-4-methylpent-3-en-2-one (49.5 g, 0.325 mol) and copper (I) iodide (61.9 g, 0.325 mol) in 700 mL of anhydrous diethyl ether at 0° C. was added a solution of 2-methyl-5-fluorophenyl magnesium bromide (0.5 M in THF, 706 mL, 0.353 mol) dropwise over 1.5 hours. The mixture was warmed to room temperature and stirred for a total of 18 hours. The reaction was quenched by addition of 500 mL of cold saturated ammonium chloride (NH4Cl) solution and the layers were separated. The aqueous layer was extracted with two 300 mL portions of diethyl ether. The combined organic fractions were washed with 300 mL of saturated ammonium chloride solution, three 300 mL portions of water and one 200 mL portion of brine, dried over magnesium sulfate, filtered, and concentrated in vacuo. Purification by column chromatography with silica gel (eluted with hexanes) afforded 1,1,1-trifluoro-4-(5-fluoro-2-methylphenyl)-4-methylpentan-2-one (68.1 g, 80%).

Provenance & Evidence