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

HRID 333946ノート

反応式

HRID 333946 の反応式
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]

参加物

8

反応物 4

HCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 935602-Chloro-2,2-difluoroacetaldehyde2 回HCID 866915952-Diethoxyphosphoryl-1-[4-(4-quinolyl)piperazin-1-yl]ethanone

生成物 2

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

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

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%).

後処理

  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)

出典と根拠

ORDレコード
ord-4c1d92d7f5d24620a11bc1003c227871
出典データセット
uspto-grants-2014_11
特許番号
US08883791B2

反応ノート

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