1-(5-bromo-2,4-difluorophenyl)ethanone

反応条件: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 1-(5-bromo-2,4-difluorophenyl)ethanone (4.9 g) in ethylene glycol (15 ml) was added hydrazine monohydrate (1.2 g) at room temperature, and the mixture was stirred at 160° C. for 26 hr. The reaction mixture was cooled to room temperature, and the insoluble material was removed. The filtrate was added to water, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous ammonium chloride solution, saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (3.2 g). The reaction mixture was cooled to room temperature the insoluble material was removed The filtrate was added to water the mixture was extracted with ethyl acetate The organic layer was washed with saturated aqueous ammonium chloride solution, saturated aqueous sodium hydrogen carbonate solution and saturated brine dried over anhydrous magnesium sulfate concentrated under reduced pressure The residue was purified by silica gel column chromatography (hexane/ethyl acetate)

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 1-(5-bromo-2,4-difluoro-phenyl)-ethanone (19 g, 64.7 mmoles, 1 equiv.) and (R)-2-methyl-propane-2-sulfinic acid amide (10.2 g, 84.1 mmoles, 0.76 equiv) in THF (0.3 M, 215 mL) is added Ti(OEt)4 (29.5 g, 129 mmoles, 2.0 equiv) in a single portion at ambient temperature. The reaction is heated to 70° C. and allowed to stir 18 h. The reaction is cooled to ambient temperature, and poured into water. The resulting suspension is filtered through a pad of diatomaceous earth and washed with ethyl acetate. The filtrate is collected and extracted with ethyl acetate. The organic layers are combined, dried over sodium sulfate, filtered, and concentrated under reduced pressure to give a residue. The residue is purified by silica gel chromatography, eluting with a linear gradient of hexane to hexane:ethyl acetate (3:1) over 20 minutes to give the title compound (81% yield): MS (m/z): 338, 340 (M+1). The reaction is cooled to ambient temperature The resulting suspension is filtered through a pad of diatomaceous earth washed with ethyl acetate The filtrate is collected extracted with ethyl acetate dried over sodium sulfate filtered concentrated under reduced pressure to give a residue The residue is purified by silica gel chromatography eluting with a linear gradient of hexane to hexane:ethyl acetate (3:1) over 20 minutes

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of AlCl3 (1040 g, 7878.7 mmol) in 1-bromo-2,4-difluorobenzene ([CAS 348-57-2], 600 g, 3108.9 mmol) was stirred for 10 min at 60° C. Acetyl chloride [CAS 75-36-5], 366 g, 4662.4 mmol) was added dropwise in the reaction mixture for 4 h at 60° C. The mixture was stirred an additional 6 h at 95° C. The reaction mixture was cooled to −10° C. Ice (2450 g) was added for 1.5 h. HCl (12 N, 1500 mL) was added and the mixture was stirred for 1 h. EtOAc (9000 mL) was added and the organic layer was washed with water, dried over Na2SO4 and filtered. After concentration, the residue was purified by column chromatography over silica gel (eluent: petroleum ether/EtOAc, 50/1) to yield I-18 (300 g, 41%). The mixture was stirred an additional 6 h at 95° C The reaction mixture was cooled to −10° C the mixture was stirred for 1 h the organic layer was washed with water dried over Na2SO4 filtered After concentration the residue was purified by column chromatography over silica gel (eluent: petroleum ether/EtOAc, 50/1) to yield I-18 (300 g, 41%)