Chloroform → 4-Bromo-1-methoxyisoquinoline

HRID 1921328Notes

Reaction equation

HRID 1921328 reaction equation
[Br:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5](=[O:12])[NH:4][C:3]=1C.[CH:14](Cl)(Cl)Cl.IC>C(=O)([O-])[O-].[Ag+2].C(N(CC)CC)C>[Br:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][CH3:14])=[N:4][CH:3]=1

Participants

6

Reactant 3

HCID 6212ChloroformHCID 6328Methyl iodideHCID 67492305HCID 67492305, compound

Product 1

HCID 247666564-Bromo-1-methoxyisoquinolineYield 60%

Reagents, catalysts & solvents 2

HCID 178418647HCID 178418647, compoundCatalystHCID 8471TriethylamineSolvent

Procedure

To a stirred suspension of 4-bromo-3-methyl-2H-isoquinolin-1-one (1.86 g, 7.81 mmol), silver carbonate (2.92 g, 10.6 mmol) and chloroform (150 mL) is added dropwise over 10 min iodomethane (7.3 mL, 117 mmol) and the mixture is stirred in the dark for 3 d. Triethylamine is added and the solids are removed by filtration through a pad of Celite. The filtrate is concentrated and the residue is purified by chromatography eluting with dichloromethane. Product containing fractions are combined and concentrated to afford 4-bromo-1-methoxyisoquinoline (1.19 g, 60% yield) as an oil that solidified on standing. LC/MS: MS m/e=252/254 (M+H); RT 4.68; 1H NMR (CDCl3, δ ppm) 8.19 (1H, d), 8.09 (1H, d), 7.71 (1H, t), 7.50 (1H, t), 4.10 (3H, s); 2.71 (3H, s).

Workup

  1. customthe solids are removed by filtration through a pad of Celite
  2. concentrationThe filtrate is concentrated
  3. customthe residue is purified by chromatography
  4. washeluting with dichloromethane
  5. additionProduct containing fractions
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-86b3369fd6614ea9a04def80da64e725
Source dataset
uspto-grants-2012_05
Patent number
US08173682B2

Reaction notes

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