Dimethylamine → N-(Dimethylaminomethyl)-indole

HRID 1957924Notes

Reaction equation

HRID 1957924 reaction equation
[CH2:1]=O.[CH3:3][NH:4][CH3:5].[NH:6]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:8]=[CH:7]1>ClCCl>[CH3:3][N:4]([CH2:1][N:6]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:8]=[CH:7]1)[CH3:5]

Participants

5

Reactant 3

HCID 674DimethylamineHCID 712FormaldehydeHCID 798Indole2×

Product 1

HCID 4342596N-(Dimethylaminomethyl)-indoleYield 57%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Formaldehyde (37% in water, 0.19 mL, 2.6 mmol) was added to cooled (ice/water bath) aqueous dimethylamine (40% in water, 0.32 mL, 2.6 mmol). The mixture was stirred for 10 min and then indole 31 (0.3 g, 2.6 mmol) was added. The suspension was stirred for 1 h in an ice/water bath and then 24 h at RT. Indole was not completely dissolved. Dichloromethane (10 mL) was added and the organic layer was separated. The solvent was evaporated and the residue was chromatographed on a Chromatotron with dichloromethane/hexanes, 5:2 mixture as eluent to remove non-polar impurities. This was followed by elution with dichloromethane/EtOAc, 5:1 to 1:1. Appropriate fractions were collected to give indole Mannich base 32 as an oil (0.25 g, 57%) which was pure by TLC.

Workup

  1. stirringThe suspension was stirred for 1 h in an ice/water bath
  2. custom24 h
  3. customat RT
  4. customthe organic layer was separated
  5. customThe solvent was evaporated
  6. customthe residue was chromatographed on a Chromatotron with dichloromethane/hexanes, 5:2 mixture as eluent
  7. customto remove non-polar impurities
  8. washThis was followed by elution with dichloromethane/EtOAc, 5:1 to 1:1
  9. customAppropriate fractions were collected

Sources & evidence

ORD record
ord-a1ec978db87b4ac28cf4b38496f50490
Source dataset
uspto-grants-2013_04
Patent number
US08410075B2

Reaction notes

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