Hydrochloric Acid → HCID 68831716, compound

HRID 1986443Notes

Reaction equation

HRID 1986443 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Br[C:48]1[CH:49]=[C:50]2[C:55](=[CH:56][CH:57]=1)[N:54]=[C:53]([CH2:58][CH:59]([CH3:61])[CH3:60])[C:52]([C:62]#[N:63])=[C:51]2[C:64]1[CH:69]=[CH:68][CH:67]=[CH:66][C:65]=1[F:70].[C:71]([OH:75])([CH3:74])([CH3:73])[CH3:72].CC(C)([O-])C.[Na+].Cl>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1>[C:71]([O:75][C:48]1[CH:49]=[C:50]2[C:55](=[CH:56][CH:57]=1)[N:54]=[C:53]([CH2:58][CH:59]([CH3:61])[CH3:60])[C:52]([C:62]#[N:63])=[C:51]2[C:64]1[CH:69]=[CH:68][CH:67]=[CH:66][C:65]=1[F:70])([CH3:74])([CH3:73])[CH3:72]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 6386tert-ButanolHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 68832559HCID 68832559, compound

Product 1

HCID 68831716HCID 68831716, compoundYield 82%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent2×

Conditions

Temperature
40 °C

Procedure

Palladium acetate (0.015 g, 0.65 mmol) and racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.12 g, 0.19 mmol) were added to toluene (10 ml) under a nitrogen atmosphere and the mixture was stirred at 40° C. for 30 min. The reaction mixture was cooled to room temperature and 6-bromo-4-(2-fluorophenyl)-2-isobutylquinoline-3-carbonitrile (0.50 g, 1.30 mmol), tert-butanol (0.25 ml, 2.61 mmol) and sodium tert-butoxide (0.188 g, 1.96 mmol) were added, and the mixture was stirred under a nitrogen atmosphere at 90° C. for 1 hr. The reaction mixture was cooled and 0.1N hydrochloric acid (10 ml) was added and the mixture was stirred at room temperature for 30 min. Toluene (50 ml) was added to the reaction mixture. The organic layer was washed with water (10 ml), and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography and crystallized from n-hexane to give 6-tert-butoxy-4-(2-fluorophenyl)-2-isobutylquinoline-3-carbonitrile (0.40 g; yield 82%) as pale-yellow crystals.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. stirringthe mixture was stirred under a nitrogen atmosphere at 90° C. for 1 hr
  3. temperatureThe reaction mixture was cooled
  4. stirringthe mixture was stirred at room temperature for 30 min
  5. washThe organic layer was washed with water (10 ml)
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customThe solvent was evaporated under reduced pressure
  8. customthe residue was purified by silica gel column chromatography
  9. customcrystallized from n-hexane

Sources & evidence

ORD record
ord-b3cebbaf20ff40a9808cdfc8df3c15b7
Source dataset
uspto-grants-2009_06
Patent number
US07547710B2

Reaction notes

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