1-Bromo-3-chloropropane → 4-(3-chloropropoxy)-1H-indole

HRID 1066070Notes

Reaction equation

HRID 1066070 reaction equation
[H-].[Na+].[OH:3][C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[CH:6]=[CH:7][NH:8]2.Br[CH2:14][CH2:15][CH2:16][Cl:17]>CN(C)C=O.O>[NH:8]1[C:9]2[C:5](=[C:4]([O:3][CH2:14][CH2:15][CH2:16][Cl:17])[CH:12]=[CH:11][CH:10]=2)[CH:6]=[CH:7]1

Participants

6

Reactant 3

HCID 80061-Bromo-3-chloropropaneHCID 24758Sodium hydrideHCID 754211H-indol-4-ol

Product 1

HCID 116941694-(3-chloropropoxy)-1H-indoleYield 59%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

A suspension of 1.6 gm (39.7 mMol) sodium hydride (60% dispersion in mineral oil) in 80 mL dimethylformamide was cooled to 0° C. under a nitrogen atmosphere. To this suspension were added 5.0 gm (37.6 mMol) 4-hydroxyindole in portions over 30 minutes. The reaction mixture was stirred at room temperature for 1.5 hours after this addition was complete. To the resulting mixture was then added dropwise a solution of 5.91 gm (37.6 mMol) 1-bromo-3-chloropropane in dimethylformamide and the reaction mixture stirred for 18 hours at room temperature. The reaction mixture was diluted with water and then extracted well with ethyl acetate. The ethyl acetate phases were combined, washed sequentially with water and saturated aqueous sodium chloride, dried over sodium sulfate and concentrated under reduced pressure. The residue was subjected to flash silica gel chromatography, eluting with 10% ethyl acetate in hexane. Fractions containing product were combined and concentrated under reduced pressure to provide 4.62 gm (59%) of the title compound.

Workup

  1. additionafter this addition
  2. stirringthe reaction mixture stirred for 18 hours at room temperature
  3. extractionextracted well with ethyl acetate
  4. washwashed sequentially with water and saturated aqueous sodium chloride
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. washeluting with 10% ethyl acetate in hexane
  8. additionFractions containing product
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-bc19113803de4785a35aa54a88e2f0f8
Source dataset
uspto-grants-2001_06
Patent number
US06242450B1

Reaction notes

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