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

HRID 593301Notes

Reaction equation

HRID 593301 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 of 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, and aqueous layer was extracted with ethyl acetate (2×100 mL). The combined organic layer was washed with water and brine solution, dried over Na2SO4 and filtered. The filtrate was concentrated under vacuum and purified by silica gel flash column chromatography using 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 (t, J=6.4 Hz, 2H).

Workup

  1. temperatureThe reaction mixture was cooled to 0° C. in ice bath
  2. extractionwas extracted with ethyl acetate (2×100 mL)
  3. washThe combined organic layer was washed with water and brine solution
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated under vacuum
  7. custompurified by silica gel flash column chromatography

Sources & evidence

ORD record
ord-40a8fa73a4ba467fafdd83ad90643add
Source dataset
uspto-grants-2016_01
Patent number
US09242929B2

Reaction notes

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