ethyl 3-(2,4-difluorophenyl)-3-oxopropanoate

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

実験手順: 41.4 g of the crude diethyl (2,4-difluorobenzoyl)malonate in 130 ml of water and 170 mg of p-toluenesulphonic acid are refluxed for 8.5 hours. The mixture is extracted using methylene chloride, and the methylene chloride phase is washed with water, dried over sodium sulphate and concentrated in vacuo. The mixture is extracted the methylene chloride phase is washed with water dried over sodium sulphate 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 solution of ethyl 3-(2,4-difluorophenyl)-3-oxopropionate (9 g, 39.4 mmol) in 1,2-dimethoxyethane (50 ml) was added sodium hydride (60% in oil, 1.58 g, 39.4 mmol) under ice-cooling and the mixture was stirred at room temperature for 30 min. To the reaction solution was dropwise added a solution of 4-trifluoromethylbenzyl bromide (9.43 g, 39.4 mmol) in 1,2-dimethoxyethane (50 ml) and the reaction solution was stirred at room temperature for 3 hrs. The reaction solution was poured into water (200 ml) and extracted with ethyl acetate (200 ml×2). The extract was washed with water and saturated brine, dried over anhydrous magnesium sulfate and evaporated under reduced-pressure. The residue was purified by silica gel column chromatography (toluene:hexane=1:1-toluene) and recrystallized from diisopropyl ether-hexane to give ethyl 3-(2,4-difluorophenyl)-3-oxo-2-((4-(trifluoromethyl)phenyl)methyl)propionate (11.6 g, 77%). cooling the reaction solution was stirred at room temperature for 3 hrs extracted with ethyl acetate (200 ml×2) The extract was washed with water and saturated brine dried over anhydrous magnesium sulfate evaporated under reduced-pressure The residue was purified by silica gel column chromatography (toluene:hexane=1:1-toluene) recrystallized from diisopropyl ether-hexane

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

実験手順: To a solution of 2,4-difluorobenzoic acid (10 g, 63.3 mmol) in tetrahydrofuran (150 ml) was added 1,1′-carbonylbis-1H-imidazole (11.3 g, 69.6 mmol) and the mixture was stirred at room temperature for 30 min. Monoethyl malonate magnesium salt (10 g, 34.8 mmol) was added to the reaction solution and the mixture was stirred at room temperature for 2 hrs. To the reaction solution were added ethyl acetate (50 ml) and water (50 ml), and conc. hydrochloric acid was added until the aqueous layer showed acidic pH. The reaction solution was extracted with ethyl acetate (200 ml×2). The extract-was washed with saturated brine, dried-over anhydrous magnesium sulfate and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1) to give ethyl 3-(2,4-difluorophenyl)-3-oxopropionate (9.85 g, 74%) as a brown oil. the mixture was stirred at room temperature for 2 hrs was added until the aqueous layer The reaction solution was extracted with ethyl acetate (200 ml×2) The extract-was washed with saturated brine, dried-over anhydrous magnesium sulfate evaporated under reduced pressure The residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1)