Benzyl Chloride → [2-(1-Benzyl-5-iodo-1h-indol-3-yl)-ethyl]-dimethyl-amine

HRID 507368Notes

Reaction equation

HRID 507368 reaction equation
[I:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][CH2:12][N:13]([CH3:15])[CH3:14].[CH2:16](Cl)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>CN(C=O)C.[H-].[Na+]>[CH2:16]([N:7]1[C:8]2[C:4](=[CH:3][C:2]([I:1])=[CH:10][CH:9]=2)[C:5]([CH2:11][CH2:12][N:13]([CH3:14])[CH3:15])=[CH:6]1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

5

Reactant 2

HCID 7503Benzyl ChlorideHCID 136913602-(5-Iodo-1H-indol-3-yl)-N,N-dimethylethanamine

Product 1

HCID 10092601[2-(1-Benzyl-5-iodo-1h-indol-3-yl)-ethyl]-dimethyl-amineYield 63.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 24758Sodium hydrideSolvent

Conditions

Temperature
4 °C

Procedure

To a solution of [2-(5-iodo-1H-indol-3-yl)-ethyl]-dimethyl-amine (Reference Example 5) (35.0 g, 111.4 mmol) in DMF (250 mL), sodium hydride is added (2.81 g, 117 mmol) at RT in portions during 15 minutes. The mixture is then stirred for another 15 minutes, and then cooled to 4° C. A solution of benzyl chloride (14.1 g, 111.4 mmol) in DMF (50 mL) is added during 20 minutes, and the temperature is maintained during 4 to 8° C. The mixture is left stirring over night, and then most of the solvent is removed on the rotavapor. To the residue is added water (500 mL), and the product is extracted with TBME (2×250 mL). The organic layer is washed with brine (2×250 mL), and after removal of the solvent, 28.5 g of a brown oil is obtained. This is dissolved in ethyl acetate (500 mL) and the product is extracted with 4 N Hcl (550 mL). The product is liberated by adding 30% NaOH to the aqueous layer (300 mL), and re-extracted into ethyl acetate (500 mL). The organic layer is washed with brine (2×250 mL), and the solvent removed to leave 20.2 g of brown oil, which is crystallized from di-isopropyl ether and pentane to give the title product (17.3 g, 38%). Concentrating the aqueous layer of the first gives a precipitate (18.8 g), which is recrystallized from ethyl acetate (250 mL) to give 12.3 g of the N-benzyl ammonium chloride of the target.

Workup

  1. temperaturethe temperature is maintained during 4 to 8° C
  2. waitThe mixture is left
  3. stirringstirring over night
  4. custommost of the solvent is removed on the rotavapor
  5. additionTo the residue is added water (500 mL)
  6. extractionthe product is extracted with TBME (2×250 mL)
  7. washThe organic layer is washed with brine (2×250 mL)
  8. customafter removal of the solvent

Sources & evidence

ORD record
ord-c353e4eee2b246679f0318833086f7ae
Source dataset
uspto-grants-2010_08
Patent number
US07786156B2

Reaction notes

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