2-Methoxypropene → 2-(5-Bromo-1H-indol-1-yl)ethanol

HRID 413739Notes

Reaction equation

HRID 413739 reaction equation
Br[CH2:2][CH2:3][OH:4].COC(C)=C.[Br:10][C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[NH:16][CH:15]=[CH:14]2.[H-].[Na+]>C1COCC1.CN(C=O)C>[OH:4][CH2:3][CH2:2][N:16]1[C:17]2[C:13](=[CH:12][C:11]([Br:10])=[CH:19][CH:18]=2)[CH:14]=[CH:15]1

Participants

7

Reactant 4

HCID 83002-MethoxypropeneHCID 108982-BromoethanolHCID 24758Sodium hydrideHCID 249055-Bromoindole

Product 1

HCID 106576502-(5-Bromo-1H-indol-1-yl)ethanolYield 61%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Under a N2 atmosphere, 2-bromoethanol (17.6 g, 141 mmol) and 2-methoxypropene (10.1 g, 141 mmol) were stirred in 71 mL of THF at 0° C. for 30 minutes The resulting solution was added to a stirring mixture of 5-bromoindole (22.83 g, 116 mmol) and 60% NaH (4.62 g, 193 mmol) in 40 mL of DMF and 60 mL of THF. The solution was stirred at ambient temperature for 4 hours. The reaction mixture was worked up by quenching the excess of NaH with water and removing the aqueous layer. The organic layer was vigorously stirred with 200 mL of 2% aqueous phosphoric acid for 5 hours when the layers were separated. The organic layer was washed with water (2×200 mL) and the solvent removed. The residue was purified by column chromatography (30:70 EtOAc-Hex) to give 17 g of 1-(2-hydroxylethyl)-5-bromoindole.

Workup

  1. customby quenching the excess of NaH with water
  2. customremoving the aqueous layer
  3. stirringThe organic layer was vigorously stirred with 200 mL of 2% aqueous phosphoric acid for 5 hours when the layers
  4. customwere separated
  5. washThe organic layer was washed with water (2×200 mL)
  6. customthe solvent removed
  7. customThe residue was purified by column chromatography (30:70 EtOAc-Hex)

Sources & evidence

ORD record
ord-b27b670c3a2448a6898d97bb33821fc7
Source dataset
uspto-grants-2003_05
Patent number
US06569867B2

Reaction notes

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