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

HRID 2278596Notes

Reaction equation

HRID 2278596 reaction equation
C([BH3-])#N.[Na+].F[C:6]1[C:14](F)=[CH:13][CH:12]=[C:11]2[C:7]=1[CH:8]=[C:9]([CH3:16])[NH:10]2.[OH2:17]>C(O)(=O)C>[OH:17][C:6]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:7]=1[CH2:8][CH:9]([CH3:16])[NH:10]2

Participants

5

Reactant 3

HCID 962WaterHCID 5003444Sodium cyanoborohydrideHCID 131885694,5-Difluoro-2-methyl-1H-indole

Product 1

HCID 553002502-Methyl-2,3-dihydro-1H-indol-4-ol

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
5 °C

Procedure

750 mg of sodium cyanoborohydride are gradually added to a solution of 1 g of 4,5-difluoro-2-methylindole in 20 ml of acetic acid under argon cooled to a temperature of about 5° C. The reaction mixture is stirred at ambient temperature for 3 hours and 5 ml of water are added. The mixture is then concentrated under reduced pressure and the residue is taken up in ethyl acetate, 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 by silica gel chromatography, elution being carried out with an 80/20 v/v heptane/ethyl acetate mixture. 0.37 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. concentrationThe mixture is then concentrated under reduced pressure
  2. additiontreated with 60 ml of a saturated sodium hydrogen carbonate solution
  3. stirringAfter stirring for 1 hour
  4. customthe organic phase is separated
  5. extractionthe aqueous phase is extracted with 50 ml of ethyl acetate
  6. washwashed with saturated brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated to dryness under reduced pressure
  10. customThe residue is purified by silica gel chromatography, elution

Sources & evidence

ORD record
ord-ba9548c74e1f41e786b6398b6f567cb1
Source dataset
uspto-grants-2015_09
Patent number
US09133168B2

Reaction notes

Loading…