Sodium hydride → (1-Benzyl-2-methyl-1H-indol-4-yloxy)-acetic acid methyl ester

HRID 650510Notes

Reaction equation

HRID 650510 reaction equation
[OH:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([CH3:18])[N:6]2[CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[H-].[Na+].Br[CH2:22][C:23]([O:25][CH3:26])=[O:24]>CN(C=O)C.O>[CH3:26][O:25][C:23](=[O:24])[CH2:22][O:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([CH3:18])[N:6]2[CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 60984Methyl bromoacetateHCID 107523601-Benzyl-2-methyl-1H-indol-4-ol

Product 1

HCID 10804819(1-Benzyl-2-methyl-1H-indol-4-yloxy)-acetic acid methyl esterYield 88%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

4-Hydroxy-2-methyl-1-(phenylmethyl)-1H-indole (530 mg, 2.2 mmol) was added to 88 mg (2.2 mmol) of 60% NaH/mineral oil in 20 mL of DMF and the mixture stirred for 0.67 hours. Then, 0.21 mL (2.2 mmol) of methyl bromoacetate was added and stirring maintained for 17 hours. The mixture was diluted with water and extracted with ethyl acetate. The ethyl acetate solution was washed with brine, dried (MgSO4), and concentrated at reduced pressure. The residue was chromatographed on silica gel eluting with 20% EtOAc/hexane to give 597 mg (88% yield) of ((2-methyl-1-(phenylmethyl)-1H-indol-4-yl)oxy)acetic acid methyl ester, 140-143° C.

Workup

  1. stirringstirring
  2. temperaturemaintained for 17 hours
  3. extractionextracted with ethyl acetate
  4. washThe ethyl acetate solution was washed with brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated at reduced pressure
  7. customThe residue was chromatographed on silica gel eluting with 20% EtOAc/hexane

Sources & evidence

ORD record
ord-658ff5e22aa24cd1a68d4fbe7e161e93
Source dataset
uspto-grants-2001_08
Patent number
US06274578B1

Reaction notes

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