Sodium hydride → 1-(5-tert-butyl-2-methoxybenzyl)-5-chloro-1H-indole-2-carboxylic acid ethyl ester

HRID 2242352Notes

Reaction equation

HRID 2242352 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].Br[CH2:19][C:20]1[CH:25]=[C:24]([C:26]([CH3:29])([CH3:28])[CH3:27])[CH:23]=[CH:22][C:21]=1[O:30][CH3:31]>CN(C)C=O.O>[CH2:3]([O:5][C:6]([C:8]1[N:9]([CH2:19][C:20]2[CH:25]=[C:24]([C:26]([CH3:27])([CH3:29])[CH3:28])[CH:23]=[CH:22][C:21]=2[O:30][CH3:31])[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 3

HCID 24758Sodium hydrideHCID 78518Ethyl 5-chloroindole-2-carboxylateHCID 666189372-Bromomethyl-4-tert-butyl-1-methoxybenzene

Product 1

HCID 685506041-(5-tert-butyl-2-methoxybenzyl)-5-chloro-1H-indole-2-carboxylic acid ethyl esterYield 94%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (60% dispersion in mineral oil, 0.154 g, 3.85 mmol) was added to a solution of 5-chloro-1H indole-2-carboxylic acid ethyl ester (0.70 g, 3.14 mmol) in dimethyl formamide (8 ml) with stirring under nitrogen, followed after 1 h by 2-bromomethyl-4-tert-butyl-1-methoxybenzene (1.00 g, 3.89 mmol). After stirring for 17 h, the reaction was diluted with water (15 ml), extracted into ethyl acetate (2×30 ml), washed with water (2×30 ml), dried with magnesium sulfate and evaporated to dryness under reduced pressure. Purification was achieved by chromatography on silica using DCM as eluent to yield 1-(5-tert-butyl-2-methoxybenzyl)-5-chloro-1H-indole-2-carboxylic acid ethyl ester as an off-white solid (1.18 g, 2.95 mmol, 94%).

Workup

  1. stirringAfter stirring for 17 h
  2. extractionextracted into ethyl acetate (2×30 ml)
  3. washwashed with water (2×30 ml)
  4. dry with materialdried with magnesium sulfate
  5. customevaporated to dryness under reduced pressure
  6. customPurification

Sources & evidence

ORD record
ord-3f248a6bf9524d498ee8eb4be4a45b85
Source dataset
uspto-grants-2010_03
Patent number
US07671080B2

Reaction notes

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