1-Bromohexane → 6-Bromo-2-(2-phenylpropyl)-isoquinolin-1-one

HRID 2403057Notes

Reaction equation

HRID 2403057 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8]([OH:12])=[N:7][CH:6]=[CH:5]2.[CH2:13](Br)[CH2:14][CH2:15][CH2:16][CH2:17]C.[OH-].[Na+].[CH3:22][C:23](OC)([CH3:25])[CH3:24]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[N:7]([CH2:22][CH:23]([C:25]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[CH3:24])[CH:6]=[CH:5]2

Participants

7

Reactant 4

HCID 81011-BromohexaneHCID 14798Sodium HydroxideHCID 15413tert-Butyl methyl etherHCID 178517609HCID 178517609, compound

Product 1

HCID 667325006-Bromo-2-(2-phenylpropyl)-isoquinolin-1-oneYield 32%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 1140TolueneSolvent

Procedure

6-Bromo-1-hydroxyisoquinoline (200 mg, 0.89 mmol, 1.0 equiv), tetrabutylammonium bromide (30 mg, 0.09 mmol, 0.1 equiv), and hexyl bromide (150 uL, 1.1 mmol, 1.2 equiv) were combined in toluene (10 mL) and treated with 50% aq. NaOH (2 mL), and the resulting mixture was stirred rapidly at ambient temperature. After an additional 14 hours of stirring at room temperature, the mixture was diluted with MTBE and washed with water, sat. NaHCO3, and brine. The organic phase was dried over Na2SO4. Addition of silica gel, concentration, and purification of the residue using flash silica gel chromatography (gradient of 3-12% ethyl acetate/hexanes) gave 6-bromo-2-(2-phenylpropyl)-isoquinolin-1-one (87 mg, 0.28 mmol, 32%) as white crystals. This isoquinolinone (87 mg, 0.28 mmol) was converted, via Methods 1 and 2, to compound 7 (27 mg, 35%) which was isolated as a white solid. [M-H]-=372.2 m/z. Activity: A

Workup

  1. stirringAfter an additional 14 hours of stirring at room temperature
  2. washwashed with water, sat. NaHCO3, and brine
  3. dry with materialThe organic phase was dried over Na2SO4
  4. additionAddition of silica gel, concentration, and purification of the residue

Sources & evidence

ORD record
ord-ba5a63e3e22647119b404656e5c6813b
Source dataset
uspto-grants-2014_08
Patent number
US08802064B2

Reaction notes

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