Sodium Hydroxide → HCID 66835573, compound

HRID 333946Notes

Reaction equation

HRID 333946 reaction equation
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]

Participants

8

Reactant 4

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

Product 2

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

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

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%).

Workup

  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)

Sources & evidence

ORD record
ord-4c1d92d7f5d24620a11bc1003c227871
Source dataset
uspto-grants-2014_11
Patent number
US08883791B2

Reaction notes

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