Dimethylformamide → [2-(7-(methoxycarbomethoxy)-1H-indol-3-yl)-1,1-dimethyl-ethyl]-carbamic acid tert-butyl ester

HRID 8125

Reaction equation

HRID 8125 reaction equation
[C:1]([O:5][C:6](=[O:22])[NH:7][C:8]([CH3:21])([CH3:20])[CH2:9][C:10]1[C:18]2[C:13](=[C:14](O)[CH:15]=[CH:16][CH:17]=2)[NH:12][CH:11]=1)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH3:25][O:26][C:27](=[O:30])CCl.CN(C)[CH:33]=[O:34]>>[C:1]([O:5][C:6](=[O:22])[NH:7][C:8]([CH3:21])([CH3:20])[CH2:9][C:10]1[C:18]2[C:13](=[C:14]([C:27]([O:26][CH2:25][O:34][CH3:33])=[O:30])[CH:15]=[CH:16][CH:17]=2)[NH:12][CH:11]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 7295Methyl chloroacetateHCID 24758Sodium hydrideHCID 69519112[2-(7-hydroxy-1H-indol-3-yl)-1,1-dimethyl-ethyl]-carbamic acid tert-butyl ester

Product 1

HCID 69517575[2-(7-(methoxycarbomethoxy)-1H-indol-3-yl)-1,1-dimethyl-ethyl]-carbamic acid tert-butyl esterYield 30%

Procedure

A solution of [2-(7-hydroxy-1H-indol-3-yl)-1,1-dimethyl-ethyl]-carbamic acid tert-butyl ester (609 mg, 2.0 mmol) is dissolved in dry dimethylformamide (30 ml) under a nitrogen atmosphere and treated with sodium hydride (84 mg, 2.1 mmol, 60% dispersion in oil) added portion-wise over a 10 minute period. The mixture is cooled in an ice/water bath and methyl-2-chloroacetate (434 mg, 4.0 mmol) is added drop-wise over 20 minutes. The ice bath is removed and the mixture stirred at room temperature for 15 hours. The reaction is then quenched with saturated brine and extracted with ethyl acetate. The ethyl acetate layer is dried and concentrated to give a crude residue, which is purified by silica gel chromatography (gradient elution, chloroform with 1%–10% of 20% methanol in acetonitrile) to give 230 mg of [2-(7-(methoxycarbomethoxy)-1H-indol-3-yl)-1,1-dimethyl-ethyl]-carbamic acid tert-butyl ester (30%).

Workup

  1. additionadded portion-wise over a 10 minute period
  2. temperatureThe mixture is cooled in an ice/water bath
  3. customThe ice bath is removed
  4. customThe reaction is then quenched with saturated brine
  5. extractionextracted with ethyl acetate
  6. dry with materialThe ethyl acetate layer is dried
  7. concentrationconcentrated
  8. customto give a crude residue, which
  9. customis purified by silica gel chromatography (gradient elution, chloroform with 1%–10% of 20% methanol in acetonitrile)

Sources & evidence

ORD record
ord-862fad865d5d4554aecfa4b466bec1e1
Source dataset
uspto-grants-2006_08
Patent number
US07087635B2

Linked notes

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