Water → (4-Bromo-2-fluorophenyl)[4-(3,5-dimethylpyridin-2-yl)piperazin-1-yl]methanone

HRID 1804012Notes

Reaction equation

HRID 1804012 reaction equation
[CH3:1][C:2]1[C:3]([N:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)=[N:4][CH:5]=[C:6]([CH3:8])[CH:7]=1.[Br:15][C:16]1[CH:24]=[CH:23][C:19]([C:20](Cl)=[O:21])=[C:18]([F:25])[CH:17]=1.[OH-].[Na+].O>O1CCCC1.C(OCC)(=O)C>[Br:15][C:16]1[CH:24]=[CH:23][C:19]([C:20]([N:12]2[CH2:11][CH2:10][N:9]([C:3]3[C:2]([CH3:1])=[CH:7][C:6]([CH3:8])=[CH:5][N:4]=3)[CH2:14][CH2:13]2)=[O:21])=[C:18]([F:25])[CH:17]=1

Participants

7

Reactant 4

HCID 962WaterHCID 14798Sodium Hydroxide2×HCID 27340264-Bromo-2-fluorobenzoyl chlorideHCID 584844961-(3,5-Dimethylpyridin-2-yl)piperazine

Product 1

HCID 58484626(4-Bromo-2-fluorophenyl)[4-(3,5-dimethylpyridin-2-yl)piperazin-1-yl]methanoneYield 88.6%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

1-(3,5-Dimethylpyridin-2-yl)piperazine (2.42 g) described in Preparation Example 47 was dissolve in tetrahydrofuran (32 mL), 4-bromo-2-fluorobenzoyl chloride (3.0 g) and 1N aqueous sodium hydroxide solution (15 mL) were added, and the mixture was stirred at room temperature. The reaction mixture poured into water under cooling, 4N aqueous sodium hydroxide solution and ethyl acetate were added and the mixture was extracted with ethyl acetate. The organic layer was washed with 4N aqueous sodium hydroxide solution and saturated brine, then washed with saturated brine, sodium sulfate was added and dried. The solvent was evaporated under reduced pressure. The residue was purified by column chromatography (ethyl acetate:hexane) to give the title compound (4.39 g).

Workup

  1. temperatureunder cooling
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe organic layer was washed with 4N aqueous sodium hydroxide solution and saturated brine
  4. washwashed with saturated brine, sodium sulfate
  5. additionwas added
  6. customdried
  7. customThe solvent was evaporated under reduced pressure
  8. customThe residue was purified by column chromatography (ethyl acetate:hexane)

Sources & evidence

ORD record
ord-ff96bda4610a4212a77e832217349d6b
Source dataset
uspto-grants-2013_01
Patent number
US08354401B2

Reaction notes

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