Water → 2-Methyl-2,3-dihydro-1H-indol-4-ol

HRID 2278590Notes

Reaction equation

HRID 2278590 reaction equation
C([BH3-])#N.[Na+].[OH:5][C:6]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:7]=1[CH:8]=[C:9]([CH3:15])[NH:10]2.O>C(O)(=O)C>[OH:5][C:6]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:7]=1[CH2:8][CH:9]([CH3:15])[NH:10]2

Participants

5

Reactant 3

HCID 962WaterHCID 5902254-Hydroxy-2-methylindoleHCID 5003444Sodium cyanoborohydride

Product 1

HCID 553002502-Methyl-2,3-dihydro-1H-indol-4-olYield 85.8%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
14 °C

Procedure

1.35 g of sodium cyanoborohydride are gradually added to a solution of 1 g of 4-hydroxy-2-methylindole in 35 ml of acetic acid under argon cooled to a temperature of about 14° C. The reaction mixture is stirred at a temperature of about 14° C. for 15 minutes, and is then allowed to warm up to ambient temperature. After 1.5 hours, the reaction mixture is treated with 15 ml of water, stirred at ambient temperature for 1 hour, and then concentrated to dryness under reduced pressure. The residue is taken up in 75 ml of ethyl acetate and then treated with 60 ml of a saturated sodium hydrogen carbonate solution. After stirring for 1 hour and then settling out, the organic phase is separated and the aqueous phase is extracted with 50 ml of ethyl acetate. The organic phases are combined, washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and then concentrated to dryness under reduced pressure. The residue is purified on a 70 g cartridge of 15-40 μm silica, elution being carried out with an 80/20 v/v cyclohexane/ethyl acetate mixture, with a flow rate of 80 ml/min. 0.87 g of 4-hydroxy-2-methylindoline is thus obtained in the form of a yellow oil, the characteristics of which are the following:

Workup

  1. temperatureto warm up to ambient temperature
  2. waitAfter 1.5 hours
  3. stirringstirred at ambient temperature for 1 hour
  4. concentrationconcentrated to dryness under reduced pressure
  5. additiontreated with 60 ml of a saturated sodium hydrogen carbonate solution
  6. stirringAfter stirring for 1 hour
  7. customthe organic phase is separated
  8. extractionthe aqueous phase is extracted with 50 ml of ethyl acetate
  9. washwashed with saturated brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated to dryness under reduced pressure
  13. customThe residue is purified on a 70 g cartridge of 15-40 μm silica, elution

Sources & evidence

ORD record
ord-96a19fd638634995b5574d473788e21a
Source dataset
uspto-grants-2015_09
Patent number
US09133168B2

Reaction notes

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