Trimethylamine oxide → 5-bromo-3,3-dimethyl-2,3-dihydro-1H-indole

HRID 2308238Notes

Reaction equation

HRID 2308238 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=O)[C:5]2([CH3:13])[CH3:12].B.CSC.O.C(Cl)Cl.C[N+]([O-])(C)C>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH2:6][C:5]2([CH3:13])[CH3:12]

Participants

6

Reactant 4

HCID 1145Trimethylamine oxideHCID 120527965-bromo-3,3-dimethyl-2,3-dihydro-1H-indol-2-oneHCID 12423031(Dimethyl sulfide)trihydroboronHCID 21908982Water methylene chloride

Product 1

HCID 111837195-bromo-3,3-dimethyl-2,3-dihydro-1H-indoleYield 87%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of the 5-bromo-1,3-dihydro-3,3-dimethyl-2H-indol-2-one (0.9 g, 3.7 mmol) in 20 mL THF at 0° C. was added a borane-methylsulfide complex (2M in THF, 38 mL, 75 mmol). The reaction mixture was warned to room temperature then brought to reflux for 4 hours. The mixture was cooled to room temperature and poured into H2O/CH2Cl2 and washed with 5% NaHCO3. The organic layer was washed with brine, dried (Na2SO4) and concentrated. The crude product was extracted in MeOH, trimethylamine N-oxide (2.0 g, 26.6 mmol) was added, and the solution was brought to reflux for 2 hours. The reaction mixture was cooled, concentrated and the crude residue purified by column chromatography (SiO2, methylene chloride) to afford 5-bromo-3,3-dimethyl-2,3-dihydro-1H-indole (0.074 g, 87%) as a yellow oil: 1H NMR (CDCl3) δ 1.29 (s, 6H), 3.30 (s, 2H), 3.5 (br s, 1H), 6.49 (d, J=8.8 Hz, 1H), 7.08-7.12 (mn, 2H); 13C-NMR (CDCl3) δ 27.69 (q), 42.21 (s), 62.01 (d), 110.38 (s), 111.09, 125.46, 130.09 (d), 141.03, 149.52 (s); MS (EI) m/z 225, 227 (M)+.

Workup

  1. customwas warned to room temperature
  2. temperatureto reflux for 4 hours
  3. washwashed with 5% NaHCO3
  4. washThe organic layer was washed with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. extractionThe crude product was extracted in MeOH
  8. temperatureto reflux for 2 hours
  9. temperatureThe reaction mixture was cooled
  10. concentrationconcentrated
  11. customthe crude residue purified by column chromatography (SiO2, methylene chloride)

Sources & evidence

ORD record
ord-f9619eea04a04b62b554298a1c3ccb7f
Source dataset
uspto-grants-2004_12
Patent number
US06835744B2

Reaction notes

Loading…