Diisopropylamine → 4-((6-Bromo-2,4-dichloroquinolin-3-yl)methyl)benzonitrile

HRID 928788Notes

Reaction equation

HRID 928788 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[Br:13][C:14]1[CH:15]=[C:16]2[C:21](=[CH:22][CH:23]=1)[N:20]=[C:19]([Cl:24])[CH:18]=[C:17]2[Cl:25].Br[CH2:27][C:28]1[CH:35]=[CH:34][C:31]([C:32]#[N:33])=[CH:30][CH:29]=1>C1COCC1>[Br:13][C:14]1[CH:15]=[C:16]2[C:21](=[CH:22][CH:23]=1)[N:20]=[C:19]([Cl:24])[C:18]([CH2:27][C:28]1[CH:35]=[CH:34][C:31]([C:32]#[N:33])=[CH:30][CH:29]=1)=[C:17]2[Cl:25]

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 869964-(Bromomethyl)benzonitrileHCID 534044506-Bromo-2,4-dichloroquinoline2×HCID 178418339Butyllithium

Product 1

HCID 867156224-((6-Bromo-2,4-dichloroquinolin-3-yl)methyl)benzonitrile

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

To a solution of diisopropylamine (1.40 mL, 9.96 mmol) in THF (12 mL) cooled to 0° C. was added n-butyllithium (2.5 M solution in hexanes, 3.80 mL, 9.50 mmol) dropwise via syringe. The reaction mixture was stirred at 0° C. for 10 minutes then cooled to −78° C. at which time a separate solution of 6-bromo-2,4-dichloroquinoline (1.80 g, 6.51 mmol, Intermediate 44: step b) in THF (29 mL) was added dropwise via syringe. The mixture was stirred at −78° C. for 30 minutes followed by the addition of 4-(bromomethyl)benzonitrile (1.52 g, 7.74 mmol) in THF (5 mL). After an additional 10 minutes of stirring at −78° C., the reaction was transferred to an ice bath and warmed to ambient temperature over 5 hours. The reaction was quenched with water and the aqueous phase was extracted with DCM. The organic phase was dried (Na2SO4), filtered, and concentrated. The crude product was purified by flash column chromatography (silica gel, 0-5% EtOAc-Hexanes) to provide the title compound as a white solid.

Workup

  1. additionwas added dropwise via syringe
  2. stirringThe mixture was stirred at −78° C. for 30 minutes
  3. stirringAfter an additional 10 minutes of stirring at −78° C.
  4. customthe reaction was transferred to an ice bath
  5. temperaturewarmed to ambient temperature over 5 hours
  6. customThe reaction was quenched with water
  7. extractionthe aqueous phase was extracted with DCM
  8. dry with materialThe organic phase was dried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe crude product was purified by flash column chromatography (silica gel, 0-5% EtOAc-Hexanes)

Sources & evidence

ORD record
ord-c74ce5c0719f4737a41f9bb345409f94
Source dataset
uspto-grants-2016_03
Patent number
US09290476B2

Reaction notes

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