Water → 5-chloro-1-(3-methylbenzyl)-1H-indole-2-carboxylic acid ethyl ester

HRID 2242345Notes

Reaction equation

HRID 2242345 reaction equation
[H-].[Na+].[CH2:3]([O:5][C:6]([C:8]1[NH:9][C:10]2[C:15]([CH:16]=1)=[CH:14][C:13]([Cl:17])=[CH:12][CH:11]=2)=[O:7])[CH3:4].[CH3:18][C:19]1[CH:20]=[C:21]([CH:24]=[CH:25][CH:26]=1)[CH2:22]Br.O>CN(C=O)C>[CH2:3]([O:5][C:6]([C:8]1[N:9]([CH2:18][C:19]2[CH:26]=[CH:25][CH:24]=[C:21]([CH3:22])[CH:20]=2)[C:10]2[C:15]([CH:16]=1)=[CH:14][C:13]([Cl:17])=[CH:12][CH:11]=2)=[O:7])[CH3:4]

Participants

6

Reactant 4

HCID 962WaterHCID 12099m-Xylyl bromideHCID 24758Sodium hydrideHCID 78518Ethyl 5-chloroindole-2-carboxylate

Product 1

HCID 685478555-chloro-1-(3-methylbenzyl)-1H-indole-2-carboxylic acid ethyl esterYield 103.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (60% dispersion in mineral oil, 0.44 g, 7.45 mmol) was added to a suspension of 5-chloro-1H-indole-2-carboxylic acid ethyl ester (2.00 g, 8.94 mmol) in N,N′-dimethylformamide (DMF) (20 ml) under nitrogen. The mixture was stirred for 1 h before addition of the 3-methylbenzyl bromide (2.07 g, 2.48 ml) and the reaction stirred for 17.5 h. Water was added to reaction mixture which precipitated product as a gummy solid. Supernatant liquid was decanted and the solid washed with water. The product was dissolved in dichloromethane (DCM), washed with water, dried over magnesium sulfate and concentrated. Purification by silica chromatography using DCM as eluent, yielded 5-chloro-1-(3-methylbenzyl)-1H-indole-2-carboxylic acid ethyl ester (3.03 g, 95%).

Workup

  1. customprecipitated product as a gummy solid
  2. customSupernatant liquid was decanted
  3. washthe solid washed with water
  4. dissolutionThe product was dissolved in dichloromethane (DCM)
  5. washwashed with water
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated
  8. customPurification by silica chromatography

Sources & evidence

ORD record
ord-c1f57a0000224535a27cfb3c1c0427c4
Source dataset
uspto-grants-2010_03
Patent number
US07671080B2

Reaction notes

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