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

HRID 333946노트

반응식

HRID 333946 반응식
C(OP([CH2:9][C:10]([N:12]1[CH2:17][CH2:16][N:15]([C:18]2[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[N:21]=[CH:20][CH:19]=2)[CH2:14][CH2:13]1)=[O:11])(OCC)=O)C.[H-].[Na+].[Cl:30][C:31]([F:35])([F:34])[CH:32]=O.[OH-].[Na+]>C1COCC1.O>[Cl:30][C:31]([F:35])([F:34])/[CH:32]=[CH:9]/[C:10]([N:12]1[CH2:13][CH2:14][N:15]([C:18]2[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[N:21]=[CH:20][CH:19]=2)[CH2:16][CH2:17]1)=[O:11].[Cl:30][C:31]([F:35])([F:34])/[CH:32]=[CH:9]\[C:10]([N:12]1[CH2:13][CH2:14][N:15]([C:18]2[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[N:21]=[CH:20][CH:19]=2)[CH2:16][CH2:17]1)=[O:11]

참가 물질

8

반응물 4

HCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 935602-Chloro-2,2-difluoroacetaldehyde2회HCID 866915952-Diethoxyphosphoryl-1-[4-(4-quinolyl)piperazin-1-yl]ethanone

생성물 2

HCID 66835573(Z)-4-chloro-4,4-difluoro-1-[4-(4-quinolyl)piperazin-1-yl]but-2-en-1-one수율 10%HCID 66835852(E)-4-chloro-4,4-difluoro-1-[4-(4-quinolyl)piperazin-1-yl]but-2-en-1-one수율 7%

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매

실험 절차

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%).

후처리

  1. temperaturethe temperature was raised to 45° C.
  2. stirringstirring
  3. waitwas continued for 3 hours
  4. extractionextracted with diethylether (2×)
  5. washThe combined organic phases were washed with 5% sodium bicarbonate solution, water
  6. dry with materialdried over magnesium sulfate
  7. customthe solvent was removed under reduced pressure
  8. customThe raw product was purified by preparative HPLC (gradient of water containing 0.1% ammonia and acetonitrile)

출처 및 근거

ORD 기록
ord-4c1d92d7f5d24620a11bc1003c227871
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08883791B2

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