Sodium hydride → 1-[2-(tert-Butyldimethylsilyloxy)ethyl]-6-methoxy-1H-indole

HRID 2215799Notes

Reaction equation

HRID 2215799 reaction equation
[CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6]([CH:7]=[CH:8][NH:9]2)=[CH:5][CH:4]=1.Br[CH2:13][CH2:14][O:15][Si:16]([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17].[H-].[Na+]>CN(C=O)C>[Si:16]([O:15][CH2:14][CH2:13][N:9]1[C:10]2[C:6](=[CH:5][CH:4]=[C:3]([O:2][CH3:1])[CH:11]=2)[CH:7]=[CH:8]1)([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 766596-Methoxy-1H-indoleHCID 3608067(2-Bromoethoxy)-tert-butyldimethylsilane

Product 1

HCID 219500581-[2-(tert-Butyldimethylsilyloxy)ethyl]-6-methoxy-1H-indoleYield 101.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 6-methoxy-1H-indole (7.0 g, 47.6 mmol) and (2-bromoethoxy)-tert-butyldimethylsilane (10.7 mL, 50.0 mmol) in DMF (100 mL) under nitrogen was added, portionwise, sodium hydride (65% dispersion in oil) (2.8 g, 71.4 mmol) at room temperature. The reaction mixture was stirred for 1 h, quenched with saturated aq NaHCO3 (100 mL) and diluted with EtOAc (150 mL). The organic phase was washed with water (3×150 mL), saturated aq NaHCO3 (100 mL), brine (2×100 mL), dried (MgSO4), filtered and concentrated. Flash chromatography (SiO2, 10% EtOAc/hexanes) gave the title compound (14.8 g, 98%) as a colorless oil. 1H NMR (300 MHz, CDCl3) 7.62 (d, J=7.2 Hz, 1H), 7.38 (s, 1H), 7.12 (d, J=3.1 Hz, 1H), 6.87 (d, J=7.2 Hz, 1H), 6.52 (d, J=3.1 Hz, 1H), 4.28 (m, 2H), 4.02 (m, 2H), 3.96 (s, 3H), 0.98 (s, 9H), 0.02 (s, 6H).

Workup

  1. customat room temperature
  2. customquenched with saturated aq NaHCO3 (100 mL)
  3. additiondiluted with EtOAc (150 mL)
  4. washThe organic phase was washed with water (3×150 mL), saturated aq NaHCO3 (100 mL), brine (2×100 mL)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-c2a56e6cd6774bbc99bfc3b8ffae7d37
Source dataset
uspto-grants-2006_09
Patent number
US07109229B2

Reaction notes

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