Hydrochloric Acid → (4-Butylphenyl)(isoquinolin-1-yl)methanone

HRID 1673073Notes

Reaction equation

HRID 1673073 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][CH3:11])=[CH:4][CH:3]=1.[Mg].BrCCBr.[C:17]1([C:27]#N)[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH:20]=[CH:19][N:18]=1.Cl.[OH-:30].[Na+]>CO.O1CCCC1>[CH2:8]([C:5]1[CH:6]=[CH:7][C:2]([C:27]([C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH:20]=[CH:19][N:18]=2)=[O:30])=[CH:3][CH:4]=1)[CH2:9][CH2:10][CH3:11]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 78391,2-DibromoethaneHCID 14798Sodium HydroxideHCID 3060571-IsoquinolinecarbonitrileHCID 5210591-Bromo-4-butylbenzeneHCID 5462224Magnesium

Product 1

HCID 17851496(4-Butylphenyl)(isoquinolin-1-yl)methanone

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

Under a nitrogen atmosphere, 1-bromo-4-butylbenzene (2.29 ml, 13.0 mmol) was added to a mixed solution of magnesium (338 mg, 13.9 mmol) and tetrahydrofuran (6.5 ml), and as an initiator, catalytic amount of 1,2-dibromoethane was added, and this was stirred under reflux for 10 minutes. The solution was cooled to 0° C., a tetrahydrofuran solution of 1-isoquinolinecarbonitrile (1.0 g, 6.49 mmol) was added, and was stirred for another 1 hour at room temperature, and at 70° C. for 3 hours. Subsequently, the solution was cooled again to 0° C., concentrated hydrochloric acid (2.56 ml) and methanol (11 ml) were added, and then refluxed for 2 hours. The concentrated residue was dissolved in 5 N sodium hydroxide and toluene, and was filtered through celite. The toluene layer of the filtrate was divided, washed with water, dried over magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography to give 1.72 g of the title compound.

Workup

  1. temperatureunder reflux for 10 minutes
  2. stirringwas stirred for another 1 hour at room temperature
  3. temperatureSubsequently, the solution was cooled again to 0° C.
  4. temperaturerefluxed for 2 hours
  5. filtrationtoluene, and was filtered through celite
  6. washwashed with water
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-3922315e57184c318c8e6b8c827dce6c
Source dataset
uspto-grants-2011_08
Patent number
US07999090B2

Reaction notes

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