2-chloro-2,2-difluoroacetaldehyde

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 2-Diethoxyphosphoryl-1-[4-(4-quinolyl)piperazin-1-yl]ethanone (78.3 mg, 0.2 mmol) was dissolved in anhydrous THF (1 ml), NaH was added (12 mg of a 60% dispersion in mineral oil, 0.3 mmol) and the mixture was stirred for 30 minutes at room temperature. 2-Chloro-2,2-difluoro-acetaldehyde (0.3 mmol, the solution of step D) was added, the temperature was raised to 45° C. and stirring was continued for 3 hours. The mixture was diluted with water, basified with 0.1 NaOH and extracted with diethylether (2×). The combined organic phases were washed with 5% sodium bicarbonate solution, water, dried over magnesium sulfate and the solvent was removed under reduced pressure. The raw product was purified by preparative HPLC (gradient of water containing 0.1% ammonia and acetonitrile) to yield (E)-4-chloro-4,4-difluoro-1-[4-(4-quinolyl)piperazin-1-yl]but-2-en-1-one (5 mg, 0.014 mmol, 7%) and (Z)-4-chloro-4,4-difluoro-1-[4-(4-quinolyl)piperazin-1-yl]but-2-en-1-one (7 mg, 0.02 mmol, 10%). the temperature was raised to 45° C. stirring was continued for 3 hours extracted with diethylether (2×) The combined organic phases were washed with 5% sodium bicarbonate solution, water dried over magnesium sulfate the solvent was removed under reduced pressure The raw product was purified by preparative HPLC (gradient of water containing 0.1% ammonia and acetonitrile)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 2-Diethoxyphosphoryl-1-[4-(4-quinolyl)piperazin-1-yl]ethanone (78.3 mg, 0.2 mmol) was dissolved in anhydrous THF (1 ml), NaH was added (12 mg of a 60% dispersion in mineral oil, 0.3 mmol) and the mixture was stirred for 30 minutes at room temperature. 2-Chloro-2,2-difluoro-acetaldehyde (0.3 mmol, the solution of step D) was added, the temperature was raised to 45° C. and stirring was continued for 3 hours. The mixture was diluted with water, basified with 0.1 NaOH and extracted with diethylether (2×). The combined organic phases were washed with 5% sodium bicarbonate solution, water, dried over magnesium sulfate and the solvent was removed under reduced pressure. The raw product was purified by preparative HPLC (gradient of water containing 0.1% ammonia and acetonitrile) to yield (E)-4-chloro-4,4-difluoro-1-[4-(4-quinolyl)piperazin-1-yl]but-2-en-1-one (5 mg, 0.014 mmol, 7%) and (Z)-4-chloro-4,4-difluoro-1-[4-(4-quinolyl)piperazin-1-yl]but-2-en-1-one (7 mg, 0.02 mmol, 10%). the temperature was raised to 45° C. stirring was continued for 3 hours extracted with diethylether (2×) The combined organic phases were washed with 5% sodium bicarbonate solution, water dried over magnesium sulfate the solvent was removed under reduced pressure The raw product was purified by preparative HPLC (gradient of water containing 0.1% ammonia and acetonitrile)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 2-Diethoxyphosphoryl-1-[4-(4-quinolyl)piperazin-1-yl]ethanone (78.3 mg, 0.2 mmol) was dissolved in anhydrous THF (1 ml), NaH was added (12 mg of a 60% dispersion in mineral oil, 0.3 mmol) and the mixture was stirred for 30 minutes at room temperature. 2-Chloro-2,2-difluoro-acetaldehyde (0.3 mmol, the solution of step D) was added, the temperature was raised to 45° C. and stirring was continued for 3 hours. The mixture was diluted with water, basified with 0.1 NaOH and extracted with diethylether (2×). The combined organic phases were washed with 5% sodium bicarbonate solution, water, dried over magnesium sulfate and the solvent was removed under reduced pressure. The raw product was purified by preparative HPLC (gradient of water containing 0.1% ammonia and acetonitrile) to yield (E)-4-chloro-4,4-difluoro-1-[4-(4-quinolyl)piperazin-1-yl]but-2-en-1-one (5 mg, 0.014 mmol, 7%) and (Z)-4-chloro-4,4-difluoro-1-[4-(4-quinolyl)piperazin-1-yl]but-2-en-1-one (7 mg, 0.02 mmol, 10%). the temperature was raised to 45° C. stirring was continued for 3 hours extracted with diethylether (2×) The combined organic phases were washed with 5% sodium bicarbonate solution, water dried over magnesium sulfate the solvent was removed under reduced pressure The raw product was purified by preparative HPLC (gradient of water containing 0.1% ammonia and acetonitrile)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 2-Diethoxyphosphoryl-1-[4-(4-quinolyl)piperazin-1-yl]ethanone (78.3 mg, 0.2 mmol) was dissolved in anhydrous THF (1 ml), NaH was added (12 mg of a 60% dispersion in mineral oil, 0.3 mmol) and the mixture was stirred for 30 minutes at room temperature. 2-Chloro-2,2-difluoro-acetaldehyde (0.3 mmol, the solution of step D) was added, the temperature was raised to 45° C. and stirring was continued for 3 hours. The mixture was diluted with water, basified with 0.1 NaOH and extracted with diethylether (2×). The combined organic phases were washed with 5% sodium bicarbonate solution, water, dried over magnesium sulfate and the solvent was removed under reduced pressure. The raw product was purified by preparative HPLC (gradient of water containing 0.1% ammonia and acetonitrile) to yield (E)-4-chloro-4,4-difluoro-1-[4-(4-quinolyl)piperazin-1-yl]but-2-en-1-one (5 mg, 0.014 mmol, 7%) and (Z)-4-chloro-4,4-difluoro-1-[4-(4-quinolyl)piperazin-1-yl]but-2-en-1-one (7 mg, 0.02 mmol, 10%). the temperature was raised to 45° C. stirring was continued for 3 hours extracted with diethylether (2×) The combined organic phases were washed with 5% sodium bicarbonate solution, water dried over magnesium sulfate the solvent was removed under reduced pressure The raw product was purified by preparative HPLC (gradient of water containing 0.1% ammonia and acetonitrile)