2-CHLORO-2',5'-DIFLUOROACETOPHENONE

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

実験手順: 887.3 mg (3.423 mmol) of palladium(II)-dichloride-diacetonitrile were dissolved in 325.0 ml of tetrahydrofuran. 2.243 g (8.530 mmol) of triphenylphosphine were added. The reaction mixture turned yellow and, after 6 minutes, turbid. The reaction mixture was stirred for 10 minutes at room temperature, whereafter 22.81 g (153.9 mmol) of (R)-methanesulfonic acid 1-methyl-prop-2-ynylester and 16.30 g (85.52 mmol) of 2-chloro-1-(2,5-difluoro-phenyl)-ethanone were added together with about 25 ml of totally 233.3 ml (256.6 mmol) of diethylzinc solution in toluene (1.1 M) dropwise. The temperature was permitted to rise to 36° C. The remaining diethylzinc solution was added dropwose within 12 minutes at 37–38° C., whereafter the temperature was prevented from rising over 39° C. After 40 minutes (temperature about 27° C.) the reaction mixture was poured onto 350 ml of ice-cold half-saturated aqueous sodium chloride solution, 500 ml of ethylacetate were added, the mixture was stirred for 5 minutes at room temperature, and 70 ml of 25% aqueous hydrochloric acid were added (everything in solution). The aqueous phase was washed once with 250 ml of ethyl acetate and the organic phases once with 150 ml of quarter-saturated aqueous sodium bicarbonate solution and once with 50 ml of 0.1N aqueous hydrochloric acid. The organic phases were combined, dried over sodium sulfate and evaporated to dryness. 24.85 g of (2R,3S)-1-chloro-2-(2,5-difluoro-phenyl)-3-methyl-pent-4-yne-2-ol were obtained, which were 70.5% pure and contained 86% of the stated diastereomer. Yield 83.1%. to rise to 36° C from rising over 39° C were added The aqueous phase was washed once with 250 ml of ethyl acetate dried over sodium sulfate evaporated to dryness

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

実験手順: 100.0 g (876.5 mmol) of 1,4-difluorobenzene and 90.83 ml (1139 mmol) of chloroacetyl chloride were cooled to 10° C. Within 5 minutes at 10–17° C. 153.5 g (1139 mmol) of aluminium chloride (99%) were added and the mixture warmed to room temperature. The mixture was heated for 30 minutes to 60° C. and the heating continued at this temperature for another 70 minutes. The reaction mixture was cooled to room temperature and poured onto a mixture of 0.8 l of ice and 400 ml at concentrated aqueous hydrochloric acid, extracted twice with each 500 ml of ethyl acetate, and the organic phases were washed once with 200 ml of water, three times with 400 ml of half-saturated aqueous sodium bicarbonate solution, dried over sodium sulfate, dissolved for 1 hour at 80° C. in 400 ml of n-hexane and, after the addition of 4 g of active carbon, filtered hot, stirred at room temperature and cooled to 0° C.; the crystals formed were dried at room temperature under reduced pressure to give 104 g (69%) of 2-chloro-1-(2,5-difluoro-phenyl)-ethanone. The mixture was heated for 30 minutes to 60° C. the heating continued at this temperature for another 70 minutes The reaction mixture was cooled to room temperature extracted twice with each 500 ml of ethyl acetate the organic phases were washed once with 200 ml of water, three times with 400 ml of half-saturated aqueous sodium bicarbonate solution dried over sodium sulfate dissolved for 1 hour at 80° C. in 400 ml of n-hexane after the addition of 4 g of active carbon filtered hot cooled to 0° C. the crystals formed were dried at room temperature under reduced pressure