Reaktion #421128

Reaktionsgleichung

NaOH

2-Diethoxyphosphoryl-1-[4-(4-quinolyl)piperazin-1-yl]ethanone

2-Chloro-2,2-difluoro-acetaldehyde

solution

2-Chloro-2,2-difluoro-acetaldehyde

NaH

→

(E)-4-chloro-4,4-difluoro-1-[4-(4-quinolyl)piperazin-1-yl]but-2-en-1-one

Ausbeute 7.0%

(Z)-4-chloro-4,4-difluoro-1-[4-(4-quinolyl)piperazin-1-yl]but-2-en-1-one

Ausbeute 10.0%

Lösungsmittel

THF

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturthe temperature was raised to 45° C.
2. 2
   workup.STIRRINGstirring
3. 3
   workup.WAITwas continued for 3 hours
4. 4
   Extraktionextracted with diethylether (2×)
5. 5
   WaschenThe combined organic phases were washed with 5% sodium bicarbonate solution, water
6. 6
   Trocknendried over magnesium sulfate
7. 7
   Sonstigethe solvent was removed under reduced pressure
8. 8
   SonstigeThe raw product was purified by preparative HPLC (gradient of water containing 0.1% ammonia and acetonitrile)

Vorschrift

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%).

Quelle