Sodium hydride → 4-[[1-(phenylmethyl)-1H-indol-5-yl]oxy]butanoic acid ethyl ester

HRID 2303523Notes

Reaction equation

HRID 2303523 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[CH:6]=[CH:5]2.[H-].[Na+].Br[CH2:21][CH2:22][CH2:23][C:24]([O:26][CH2:27][CH3:28])=[O:25]>CN(C=O)C.C1COCC1.O.CCOCC>[CH2:27]([O:26][C:24](=[O:25])[CH2:23][CH2:22][CH2:21][O:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)[CH:6]=[CH:5]2)[CH3:28]

Participants

8

Reactant 3

HCID 24758Sodium hydrideHCID 76300Ethyl 4-bromobutyrateHCID 107754621H-Indol-5-ol, 1-(phenylmethyl)-

Product 1

HCID 105930394-[[1-(phenylmethyl)-1H-indol-5-yl]oxy]butanoic acid ethyl esterYield 40.4%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 850 mg (4.0 mmol) of 5-hydroxy-1-(phenylmethyl)-1H-indole in 75 mL of DMF and 20 mL of THF was treated with 200 mg (5.0 mmol) of 60% NaH/mineral oil and after stirring for 0.17 hours, 0.7 mL (4.9 mmol) of ethyl 4-bromobutyrate was added. After 2.75 hours, the mixture was diluted with water and extracted with EtOAc. The EtOAc solution was washed with water, saturated NaCl solution, dried(Na2SO4) and concentrated at reduced pressure. The residue was chromatographed on silica gel and the 545 mg (40% yield) of 4-[[1-(phenylmethyl)-1H-indol-5-yl]oxy]butanoic acid ethyl ester by eluting with a gradient, 15% ether/hexaneØ50% ether/hexane.

Workup

  1. waitAfter 2.75 hours
  2. extractionextracted with EtOAc
  3. washThe EtOAc solution was washed with water, saturated NaCl solution, dried(Na2SO4)
  4. concentrationconcentrated at reduced pressure
  5. customThe residue was chromatographed on silica gel

Sources & evidence

ORD record
ord-5800338a33c44a209ebcf27e5f7e0c8c
Source dataset
uspto-grants-2002_08
Patent number
US06433001B1

Reaction notes

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