3-Methylisoquinoline → 4-Bromo-3-methyl-isoquinoline

HRID 1909051Notes

Reaction equation

HRID 1909051 reaction equation
[CH3:1][C:2]1[N:3]=[CH:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[CH:7][CH:6]=2.[Br:12]Br>Br.C(Cl)Cl.[OH-].[Na+]>[Br:12][C:11]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[N:3][C:2]=1[CH3:1]

Participants

6

Reactant 2

HCID 143063-MethylisoquinolineHCID 24408Bromine

Product 1

HCID 37777034-Bromo-3-methyl-isoquinolineYield 34.8%

Reagents, catalysts & solvents 3

HCID 260Hydrogen BromideSolventHCID 6344DichloromethaneSolventHCID 14798Sodium HydroxideSolvent

Conditions

Temperature
110 °C

Procedure

In a 40 mL screw-top vial with a stirbar was added 3-methyl-isoquinoline (6.00 g, 41.9 mmol) in hydrobromic acid (6 mL), followed by the dropwise addition of bromine (2.2 mL, 42.7 mmol, 1.02 eq). The entire suspension was heated at 100-120° C. for 24 hr. The reaction mix was cooled and diluted with DCM (100 mL) and 1N NaOH added slowly to neutralize the reaction. The organic layer was collected and dried over Na2SO4 and concentrated to a dark orange oil. The crude reaction was purified using Biotage MPLC system (40M column size, 0-15% Ethyl Acetate/Heptane over 30CV) giving a tan crystalline solid as the desire product (3.48 g, 14.57 mmol, 34.8%). 1H NMR (CDCl3, 400 MHz): δ 9.01 (s, 1H), δ 8.12-8.10 (d, 1H), δ 7.87-7.85 (d, 1H), δ7.72-7.68 (dt, 1H), δ 7.54-7.50 (dt, 1H), δ 2.80 (s, 3H); LRMS (m/z): 224, 222 (M+H).

Workup

  1. additionThe reaction mix
  2. temperaturewas cooled
  3. additionadded slowly
  4. customthe reaction
  5. customThe organic layer was collected
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated to a dark orange oil
  8. customThe crude reaction
  9. customwas purified

Sources & evidence

ORD record
ord-0758972f1d9244a283314fdbd76e2cc3
Source dataset
uspto-grants-2013_12
Patent number
US08598217B2

Reaction notes

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