Hydrochloric Acid → 5-methoxy-2,3-dihydro-1H-indole

HRID 1598001Notes

Reaction equation

HRID 1598001 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]=[CH:6]2.Cl.[OH-].[Na+].C([O-])([O-])=O.[Na+].[Na+]>C1COCC1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH2:7][CH2:6]2

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 138725-MethoxyindoleHCID 14798Sodium Hydroxide

Product 1

HCID 107019745-methoxy-2,3-dihydro-1H-indoleYield 96%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
20 °C

Procedure

To 5-methoxy-indole (4.55 g, 31 mmol) suspended in THF (10 mL) at 0°-5° C. was added borane/pyridine complex (15.5 ml of 8M in BH3) followed by dropwise aqueous 6N HCl (50 mL) over 15 min. During the addition THF was added dropwise as required to control foaming. The mixture was stirred 45 min at 20° C., the pH was raised to ~10 by the addition of aqueous NaOH and Na2CO3, and the mixture was extracted with CHCl3. The organic extracts were washed with brine at pH 9-10 dried over MgSO4(s), filtered, and concentrated in vacuo to afford 5-methoxy-indoline (96%; GC-MS: RT=min, M+ =149) which was >97% purity by 1H NMR. This material could be used without further purification, or precipitated pure as its hydrochloride salt by the addition of 1 eq. of 1N HCl in Et2O to a solution of the free base in EtOAc or ether.

Workup

  1. additionwas added borane/pyridine complex (15.5 ml of 8M in BH3)
  2. additionwas added dropwise
  3. extractionthe mixture was extracted with CHCl3
  4. washThe organic extracts were washed with brine at pH 9-10
  5. dry with materialdried over MgSO4(s)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-dec090dc826a46de929709f0a414c5a6
Source dataset
uspto-grants-1998_04
Patent number
US05736534

Reaction notes

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