1,1,1-trifluoro-4-methylpent-3-en-2-one

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of the Grignard reagent (generated from the reaction of 2-(3-bromophenyl)-[1,3]dioxane with magnesium turnings in THF, 0.25 M, 52.6 mL, 13.1 mmol) was treated with copper (I) iodide (2.5 g, 13.1 mmol) at 0° C. After 45 minutes, 1,1,1-trifluoro-4-methylpent-3-en-2-one (2 g, 13.1 mmol) was added, and the reaction mixture was slowly warmed to room temperature and stirred overnight. The mixture was quenched with aqueous saturated ammonium chloride solution and extracted with ethyl acetate. The combined organic layers were washed with aqueous saturated sodium chloride solution, dried with sodium sulfate, filtered, and concentrated in vacuo. The residue was triturated with hexanes and filtered. The filtrate was concentrated in vacuo to give 1.78 g of the crude product, which was used without purification. The mixture was quenched with aqueous saturated ammonium chloride solution extracted with ethyl acetate The combined organic layers were washed with aqueous saturated sodium chloride solution dried with sodium sulfate filtered concentrated in vacuo The residue was triturated with hexanes filtered The filtrate was concentrated in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a 2 M ether/THF solution of 1,1,1-trifluoro-4-methylpent-3-en-2-one was added 3.8 g of copper (I) iodide and 10 mL of a 2 M ether solution of 4-fluorophenylmagnesium bromide at 0° C. The mixture was warmed to room temperature and stirred for 2 hours. The reaction was quenched with saturated aqueous NH4Cl, and extracted three times with EtOAc. The combined organic layers were washed with water, brine, dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash chromatography to yield 460 mg of 1,1,1-trifluoro-4-(4-fluorophenyl)-4-methylpentan-2-one. The reaction was quenched with saturated aqueous NH4Cl extracted three times with EtOAc The combined organic layers were washed with water, brine dried over magnesium sulfate filtered concentrated in vacuo The residue was purified by flash chromatography

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a 2 M ether/THF solution of the above 1,1,1-trifluoro-4-methylpent-3-en-2-one was added 3.8 g of CuI and 10 mL of 2 M ether solution of 4-fluorophenylmagnesium bromide at 0° C. The mixture was warmed to room temperature and stirred for 2 hours. The reaction was quenched with saturated aqueous ammonium chloride and extracted with EtOAc three times. The combined organic layers were washed with water, brine, dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash chromatography to yield 460 mg of the title compound. The reaction was quenched with saturated aqueous ammonium chloride extracted with EtOAc three times The combined organic layers were washed with water, brine dried over magnesium sulfate filtered concentrated in vacuo The residue was purified by flash chromatography

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a 2 M ether/THF solution of the above 1,1,1-trifluoro-4-methylpent-3-en-2-one was added 3.8 g of CuI and 10 mL of 2 M ether solution of 4-fluorophenylmagnesium bromide at 0° C. The mixture was warmed to room temperature and stirred for 2 hours. The reaction was quenched with saturated aqueous ammonium chloride and extracted with EtOAc three times. The combined organic layers were washed with water and brine, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by flash chromatography to yield 460 mg of the title compound. The reaction was quenched with saturated aqueous ammonium chloride extracted with EtOAc three times The combined organic layers were washed with water and brine dried over magnesium sulfate filtered concentrated in vacuo The residue was purified by flash chromatography

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a 2 M ether/THF solution of the above 1,1,1-trifluoro-4-methylpent-3-en-2-one was added 3.8 g of CuI and 10 mL of 2 M ether solution of 4-fluorophenylmagnesium bromide at 0° C. The mixture was warmed to room temperature and stirred for 2 hours. The reaction was quenched with saturated aqueous ammonium chloride and extracted with EtOAc three times. The combined organic layers were washed with water and brine, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by flash chromatography to yield 460 mg of the title compound. The reaction was quenched with saturated aqueous ammonium chloride extracted with EtOAc three times The combined organic layers were washed with water and brine dried over magnesium sulfate filtered concentrated in vacuo The residue was purified by flash chromatography

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of the Grignard reagent (generated from the reaction of 2-(3-bromophenyl)-[1,3]dioxane with magnesium turnings in THF, 0.25 M, 52.6 mL, 13.1 mmol) was treated with copper (I) iodide (2.5 g, 13.1 mmol) at 0° C. After 45 minutes, 1,1,1-trifluoro-4-methylpent-3-en-2-one (2 g, 13.1 mmol) was added, and the reaction mixture was slowly warmed to room temperature and stirred overnight. The mixture was quenched with aqueous saturated ammonium chloride solution and extracted with ethyl acetate. The combined organic layers were washed with aqueous saturated sodium chloride solution, dried with sodium sulfate, filtered, and concentrated in vacuo. The residue was triturated with hexanes and filtered. The filtrate was concentrated in vacuo to give 1.78 g of the crude product, which was used without purification. The mixture was quenched with aqueous saturated ammonium chloride solution extracted with ethyl acetate The combined organic layers were washed with aqueous saturated sodium chloride solution dried with sodium sulfate filtered concentrated in vacuo The residue was triturated with hexanes filtered The filtrate was concentrated in vacuo

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 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%). The reaction was quenched by addition of 500 mL of cold saturated ammonium chloride (NH4Cl) solution 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 concentrated in vacuo Purification by column chromatography with silica gel (eluted with hexanes)