Dimethylformamide → 6-tert-Butyl indole-1-carboxylic acid tert-butyl ester

HRID 23475Notes

Reaction equation

HRID 23475 reaction equation
[C:1]([O:5][C:6](=[O:19])[NH:7][C:8]1[CH:13]=[C:12]([C:14]([CH3:17])([CH3:16])[CH3:15])[CH:11]=[CH:10][C:9]=1[CH3:18])([CH3:4])([CH3:3])[CH3:2].[C:20]([Li])(C)(C)C.CN(C=O)C>C1COCC1>[C:1]([O:5][C:6]([N:7]1[C:8]2[C:9](=[CH:10][CH:11]=[C:12]([C:14]([CH3:17])([CH3:16])[CH3:15])[CH:13]=2)[CH:18]=[CH:20]1)=[O:19])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 22217844HCID 22217844, compoundHCID 178418306HCID 178418306, compound

Product 1

HCID 539221666-tert-Butyl indole-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(5-tert-Butyl-2-methyl-phenyl)-carbamic acid tert-butyl ester (prepared in Example CC; 19.7 g, 75 mmol) in 100 mL of THF was cooled to −40° C. To it was added tert-butyllithium (1.5 M, 100 mL, 150 mmol), dropwise with stirring, at −45° C. to −35° C. After the addition was complete, the reaction was stirred at −35° C. for another 15 minutes. DMF (10.97 g, 150 mmol) was added dropwise, and the reaction mixture was stirred at −35° C. for 30 minutes, followed by slow warming to room temperature. The reaction was quenched with saturated NH4Cl solution and diluted with EtOAc. The organic layer was washed with brine, dried (MgSO4), and concentrated. The residue was dissolved in 100 mL of THF and 2 mL of concentrated HCl and stirred at room temperature for 1 hour. EtOAc was added, and the solution was washed with saturated NaHCO3 solution and brine and dried (MgSO4). Concentration gave a residue that was purified by flash silica gel chromatography (5%-50% EtOAc in hexanes). MS(APCI): 274 (M+H).

Workup

  1. customwas cooled to −40° C
  2. additionAfter the addition
  3. stirringthe reaction was stirred at −35° C. for another 15 minutes
  4. stirringthe reaction mixture was stirred at −35° C. for 30 minutes
  5. customThe reaction was quenched with saturated NH4Cl solution
  6. additiondiluted with EtOAc
  7. washThe organic layer was washed with brine
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated
  10. dissolutionThe residue was dissolved in 100 mL of THF
  11. stirring2 mL of concentrated HCl and stirred at room temperature for 1 hour
  12. additionEtOAc was added
  13. washthe solution was washed with saturated NaHCO3 solution and brine
  14. dry with materialdried (MgSO4)
  15. concentrationConcentration
  16. customgave a residue that
  17. customwas purified by flash silica gel chromatography (5%-50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-f7dace7499684a1db3afeabcd0a62410
Source dataset
uspto-grants-2005_02
Patent number
US06852711B2

Reaction notes

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