Ethyl 1H-indole-3-acetate → tert-butyl 2-bromo-3-(2-ethoxy-2-oxoethyl)-1H-indole-1-carboxylate

HRID 1471643Notes

Reaction equation

HRID 1471643 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:2]1.C1C(=O)N([Br:23])C(=O)C1.CCN(C(C)C)C(C)C.[CH3:33][C:34]([O:37][C:38]([O:40]C(OC(C)(C)C)=O)=O)([CH3:36])[CH3:35]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[Br:23][C:2]1[N:1]([C:38]([O:37][C:34]([CH3:36])([CH3:35])[CH3:33])=[O:40])[C:9]2[C:4]([C:3]=1[CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:5][CH:6]=[CH:7][CH:8]=2

Participants

7

Reactant 4

HCID 13067Ethyl 1H-indole-3-acetateHCID 67184N-bromobutanimide2×HCID 81531DiisopropylethylamineHCID 90495Di-tert-butyl dicarbonate

Product 1

HCID 90281421tert-butyl 2-bromo-3-(2-ethoxy-2-oxoethyl)-1H-indole-1-carboxylateYield 58%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

Ethyl 2-(1H-indol-3-yl)acetate (15 g, 73.9 mmol) was dissolved in DCM (750 mL). At ambient temperature, NBS (13.15 g, 73.9 mmol) was added to the reaction mixture in 5 portions approximately 2 minutes apart. After the last addition of NBS, iPr2NEt (28 mL, 162 mmol) was added slowly to the reaction mixture and stirred for 5 minutes. Boc2O (33.8 g, 155 mmol) was added followed by DMAP (900 mg). After stirring at 16 h, the reaction was partitioned between DCM and H2O. The organics were washed with aqueous 1N HCl and dried over sodium sulfate. After removal of solvent, the crude product was purified by silica gel chromatography to provide tert-butyl 2-bromo-3-(2-ethoxy-2-oxoethyl)-1H-indole-1-carboxylate (16.3 g, 58%). MS (m/z) 382 [M+H]+.

Workup

  1. additionwas added slowly to the reaction mixture
  2. stirringAfter stirring at 16 h
  3. customthe reaction was partitioned between DCM and H2O
  4. washThe organics were washed with aqueous 1N HCl
  5. dry with materialdried over sodium sulfate
  6. customAfter removal of solvent
  7. customthe crude product was purified by silica gel chromatography

Sources & evidence

ORD record
ord-5919ff02e5c54d7fb44c2ac26b094108
Source dataset
uspto-grants-2015_04
Patent number
US09012441B2

Reaction notes

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