Acetic Anhydride → 1-(2,3-Dihydro-6-methoxy-1H-indol-1-yl)ethanone

HRID 1014337Notes

Reaction equation

HRID 1014337 reaction equation
[CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6]([CH:7]=[CH:8][NH:9]2)=[CH:5][CH:4]=1.[BH3-]C#N.[Na+].[C:16](OC(=O)C)(=[O:18])[CH3:17]>C(O)(=O)C>[C:16]([N:9]1[C:10]2[C:6](=[CH:5][CH:4]=[C:3]([O:2][CH3:1])[CH:11]=2)[CH2:7][CH2:8]1)(=[O:18])[CH3:17]

Participants

5

Reactant 3

HCID 7918Acetic AnhydrideHCID 766596-Methoxy-1H-indoleHCID 5003444Sodium cyanoborohydride

Product 1

HCID 594419921-(2,3-Dihydro-6-methoxy-1H-indol-1-yl)ethanone

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent2×

Procedure

To a solution of 6-(methyloxy)-1H-indole (5.0 g, 34 mmols) in acetic acid (150 mL) was added NaBH3CN (5.12 g, 81.6 mmol) in several small portions. After stirring overnight at rt, the solvent was removed, the residue redissolved in ethyl acetate (300 mL), washed with saturated NaHCO3 (600 mL), filtered through a cotton plug and concentrated under reduced pressure to provide the crude indoline. ESIMS (M+H)+=150. The residue was then dissolved in glacial acetic acid (150 mL) and acetic anhydride (3.45 g, 33.86 mmol) was added. After stirring at rt for two hrs, the solvent was removed, residue resuspended in ethyl acetate (200 mL), washed with saturated NaHCO3 (600 mL). The aqueous layer was extracted with ethyl acetate (200 mL). The organic layers were combined, filtered through a cotton plug, and concentrated under reduced pressure to provide 1-acetyl-6-(methyloxy)-2,3-dihydro-1H-indole which was used without any further purification. ESIMS (M+H)+=192.

Workup

  1. customthe solvent was removed
  2. dissolutionthe residue redissolved in ethyl acetate (300 mL)
  3. washwashed with saturated NaHCO3 (600 mL)
  4. filtrationfiltered through a cotton plug
  5. concentrationconcentrated under reduced pressure
  6. customto provide the crude indoline
  7. stirringAfter stirring at rt for two hrs
  8. customthe solvent was removed
  9. washwashed with saturated NaHCO3 (600 mL)
  10. extractionThe aqueous layer was extracted with ethyl acetate (200 mL)
  11. filtrationfiltered through a cotton plug
  12. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-e66e4b9032c84c608f10f09633cf04f7
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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