Dimethyl Sulfate → 1-Methyl-1H-indol-5-ol

HRID 2220325Notes

Reaction equation

HRID 2220325 reaction equation
C([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([CH3:18])[CH:13]=[CH:12]2)C1C=CC=CC=1.[OH-].[K+].S([O-])([O-])(=O)=O.[Na+].[Na+].S(OC)(OC)(=O)=O>C(O)C>[CH3:18][N:14]1[C:15]2[C:11](=[CH:10][C:9]([OH:8])=[CH:17][CH:16]=2)[CH:12]=[CH:13]1

Participants

6

Reactant 4

HCID 6497Dimethyl SulfateHCID 14797Potassium HydroxideHCID 24436Sodium SulfateHCID 259196N-Methyl-5-benzyloxyindole

Product 1

HCID 108445251-Methyl-1H-indol-5-ol

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

(Ref: Taborsky, R. G.; Delvigs, P; Palaic, D; Bumpus, F. M. J. Med. Chem. (1967), 10(3), 403-7). To a solution of 5-benzyloxy-1-methyl-1H-indole (2 g, 8.9 mmol) in ethanol (20 mL) was added potassium hydroxide (0.62 g, 11.2 mmol). The resulting solution was allowed to stir at room temperature for 10 mins before evaporating the ethanol in vacuo. The residue was taken up in acetone (75 mL) and sodium sulfate (6.4 g, 44.8 mmol) was added, followed by dimethyl sulfate (0.87 mL, 8.9 mmol) via syringe. The solution was stirred for 0.5 h, then filtered and evaporated in vacuo. The resulting residue was then taken up in ethanol (50 mL) and 10% palladium on charcoal (0.4 g) was added. This solution was stirred under a hydrogen atmosphere for 4 h, then filtered through celite and the solvent evaporated in vacuo. This material was purified by flash chromatography, eluting silica gel with hexane:ethyl acetate (100:0 to 50:50) to give the product. (0.48 g, 37%); δH (300 MHz, CDCl3) 7.15 (1H, d, Ar), 7.01 (2H, m, Ar), 6.8 (1H, m, Ar), 6.32 (1H, m, Ar), 3.73 (3H, s, NCH3).

Workup

  1. custombefore evaporating the ethanol in vacuo
  2. stirringThe solution was stirred for 0.5 h
  3. filtrationfiltered
  4. customevaporated in vacuo
  5. addition10% palladium on charcoal (0.4 g) was added
  6. stirringThis solution was stirred under a hydrogen atmosphere for 4 h
  7. filtrationfiltered through celite
  8. customthe solvent evaporated in vacuo
  9. customThis material was purified by flash chromatography
  10. washeluting silica gel with hexane:ethyl acetate (100:0 to 50:50)
  11. customto give the product

Sources & evidence

ORD record
ord-3316a9d0bf064765a61679d3681c833e
Source dataset
uspto-grants-2008_08
Patent number
US07417064B2

Reaction notes

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