Dimethylformamide → 4-Bromo-[3-(tert-butyldimethylsilyloxy)propyl]-1H-indole
Reaction equation
[H-].[Na+].[Br:3][C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[CH:6]=[CH:7][NH:8]2.Br[CH2:14][CH2:15][O:16][Si:17]([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:19])[CH3:18].[CH3:24]N(C)C=O>>[Br:3][C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[CH:6]=[CH:7][N:8]2[CH2:24][CH2:14][CH2:15][O:16][Si:17]([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:19])[CH3:18]Participants
Procedure
Add sodium hydride (4.89 g, 122.4 mmol, 60% dispersion in mineral oil) to a solution of 4-Bromo-1H-indole (12 g, 61.2 mmol) in dimethylformamide (100 ml). Cool the reaction to 0° C. and add (2-bromoethoxy)-tert-butyldimethylsilane (17.04 g, 67.32 mmol). Stir the reaction for 1 hour at room temperature, quench with aqueous saturated sodium bicarbonate, and extract into ethyl acetate. Combine the organic layers and wash with saturated aqueous sodium chloride, dry over magnesium sulfate. Concentrate under reduced pressure to obtain the title compound, (22.45 g, 100%), as a clear oil. 1H NMR (400 MHz, DMSO-d6) 7.48 (d, J=8, 1H), 7.4 (d, J=3 Hz, 1H), 7.22 (d, J=8 Hz, 1H), 7.05 (dd, J=8, 1 Hz, 1H), 6.4 (d, J=3 Hz, 1H), 4.25 (t, J=7 Hz, 2H), 3.49 (t, J=7 Hz, 2H), 1.9 (quintuplet, 2H), 0.82 (s, 9H), 0.0 (s, 6H).
Workup
- temperatureCool
- customthe reaction to 0° C.
- customthe reaction for 1 hour at room temperature
- customquench with aqueous saturated sodium bicarbonate
- extractionextract into ethyl acetate
- washwash with saturated aqueous sodium chloride
- dry with materialdry over magnesium sulfate
- concentrationConcentrate under reduced pressure
Sources & evidence
- ORD record
- ord-792bd7e1c1754c6db5305d8438fbf648
- Source dataset
- uspto-grants-2008_07
- Patent number
- US07405305B2
Reaction notes
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