Methanesulfonic Acid → 6-Bromo-3,4-dihydro-2H-isoquinolin-1-one

HRID 576569Notes

Reaction equation

HRID 576569 reaction equation
[N-:1]=[N+]=[N-].[Na+].[Br:5][C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[C:11](=[O:15])[CH2:10][CH2:9]2.CS(O)(=O)=O.[OH-].[Na+]>ClCCl>[Br:5][C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[C:11](=[O:15])[NH:1][CH2:10][CH2:9]2

Participants

6

Reactant 4

HCID 6395Methanesulfonic AcidHCID 14798Sodium HydroxideHCID 33557Sodium AzideHCID 5206955-Bromo-1-indanone

Product 1

HCID 218654506-Bromo-3,4-dihydro-2H-isoquinolin-1-oneYield 60%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

NaN3 (6.2 g, 94.78 mmol) was added to a solution of 5-bromo-1-indanone (10 g, 47.39 mmol) in 40 mL mixture of methane sulphonic acid and dichloromethane (1:1) in portion wise at 0° C.-5° C. The resulting mixture was stirred for 8 h at room temperature. The reaction mixture was cooled to 0° C. in ice bath, neutralized with 5% aq. NaOH solution, and the aqueous layer with extracted with ethyl acetate (2×100 mL). The combined organic layer was washed with water and brine solution, dried over sodium sulphate, filtered and concentrated under vacuum. The residue was purified by silica gel flash column chromatography by eluting with 30% ethyl acetate in hexane to afford title compound (6.4 g, 60%) as solid. 1H NMR (400 MHz, CDCl3): δ 7.95 (d, J=8.4 Hz, 1H), 7.5 (d, J=8.4 Hz, 1H), 7.4 (s, 1H), 6.1 (bs, 1H), 3.6 (t, J=6.8 Hz, 2H), 3.0 (t, J=6.4 Hz, 2H).

Workup

  1. temperatureThe reaction mixture was cooled to 0° C. in ice bath
  2. extractionthe aqueous layer with extracted with ethyl acetate (2×100 mL)
  3. washThe combined organic layer was washed with water and brine solution
  4. dry with materialdried over sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customThe residue was purified by silica gel flash column chromatography
  8. washby eluting with 30% ethyl acetate in hexane

Sources & evidence

ORD record
ord-b989744c706c4e41be951326daa7c976
Source dataset
uspto-grants-2015_05
Patent number
US09040517B2

Reaction notes

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