2-bromo-1-(2,4-difluorophenyl)propan-1-one

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: In methylene chloride (300 ml) was dissolved 2',4'-difluoropropiophenone (55 g), to which was added bromine (50 g) dropwise, while stirring, during 30 minutes. The mixture was stirred for 30 minutes at room temperature. To the reaction mixture was added water (200 ml), and the methylene chloride layer was washed three times, followed by drying over anhydrous magnesium sulfate. The solvent was distilled off to leave 2-bromo-2',4'-difluoropropiophenone (77 g) as a pale yellow oily product. The mixture was stirred for 30 minutes at room temperature the methylene chloride layer was washed three times by drying over anhydrous magnesium sulfate The solvent was distilled off

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 300 mg of 5-[3-(tert-butyldimethylsilanyloxymethyl)phenyl]pyridin-2-ylamine dissolved in 5 ml of ethanol are placed in a screw reactor. 200 mg of sodium hydrogen carbonate and 470 mg of 2-bromo-1-(2,4-difluorophenyl)propan-1-one are added thereto. The reactor is closed and heated at 80° C. for 20 h. After cooling, the reaction mixture is concentrated under reduced pressure. The residue obtained is purified by silica gel chromatography, elution being carried out with a heptane/ethyl acetate mixture. 220 mg of compound are obtained. are placed in a screw reactor The reactor is closed After cooling the reaction mixture is concentrated under reduced pressure The residue obtained is purified by silica gel chromatography, elution

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Bromo-2',4'-difluoropropiophenone (141 g) was dissolved in methanol (1100 ml), to which was added sodium formate (176.2 g), and the mixture was stirred for 2 days at 50° C. Methanol was distilled off under reduced pressure. The residue was subjected to extraction by the addition of ethyl acetate (700 ml) and water (500 ml). The ethyl acetate layer was dried over magnesium sulfate, then the solvent was distilled off under reduced pressure. The residue was crystallized from hexane (200 ml) to afford 2',4'-difluoro-2-hydroxypropiophenone (50.5 g) as colorless prisms, m.p. 49°-51° C. Methanol was distilled off under reduced pressure The residue was subjected to extraction by the addition of ethyl acetate (700 ml) and water (500 ml) The ethyl acetate layer was dried over magnesium sulfate the solvent was distilled off under reduced pressure The residue was crystallized from hexane (200 ml)

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

Procedure: To a mixture of m-difluorobenzene (75 ml) and anhydrous aluminium chloride (115 g) was added dropwise, while stirring, 2-bromopropionyl chloride (100 g) during 50 minutes. The mixture was stirred for 2 hours on an oil bath at 50°-55° C. The reaction mixture was cooled, to which was added methylene chloride (500 ml). The resultant solution was added, in limited amounts, to ice-water (1.5 l) while stirring. The methylene chloride layer was separated, and the aqueous layer was subjected to extraction twice with methylene chloride (100 ml). The methylene chloride layers were combined and washed with water (500 ml), which was dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to leave 2-bromo-2',4'-difluoropropiophenone (142.5 g) as a pale yellow oily product. 1H-NMR (CDCl3) δ: 1.90(3H), 5.25(1H), 6.85~7.06(2H), 7.93~8.05(1H) was added dropwise The mixture was stirred for 2 hours on an oil bath at 50°-55° C The reaction mixture was cooled, to which while stirring The methylene chloride layer was separated the aqueous layer was subjected to extraction twice with methylene chloride (100 ml) washed with water (500 ml), which was dried over anhydrous magnesium sulfate The solvent was distilled off under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir: