Sodium hydride → [1-(2-trimethylsilanyl-ethoxymethyl)-1H-indol-3yl]-acetic acid methyl ester

HRID 2376212Notes

Reaction equation

HRID 2376212 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5](=[O:16])[CH2:6][C:7]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[NH:9][CH:8]=1.[CH3:17][Si:18]([CH2:21][CH2:22][O:23][CH2:24]Cl)([CH3:20])[CH3:19]>CN(C=O)C.CS(C)=O>[CH3:3][O:4][C:5](=[O:16])[CH2:6][C:7]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[N:9]([CH2:24][O:23][CH2:22][CH2:21][Si:18]([CH3:20])([CH3:19])[CH3:17])[CH:8]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 74706Methyl indole-3-acetateHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl ether

Product 1

HCID 68874684[1-(2-trimethylsilanyl-ethoxymethyl)-1H-indol-3yl]-acetic acid methyl esterYield 70%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of sodium hydride (326 mg, 8.10 mmol) in DMF (13 mL) at 0° C. was added a solution of (1H-Indol-3-yl)-acetic acid methyl ester (1.0 g, 5.3 mmol) in DMSO (3 mL). The mixture was stirred at 0° C. for 30 min and then at rt for 1 h. The reaction mixture was cooled back down to 0° C., and SEMCl (1.35 mL, 8.41 mmol) was added neat. The reaction mixture was stirred at 0° C. for 15 min and then at rt for 1 h. The reaction mixture was then partitioned between water (200 mL) and diethyl ether (200 mL) followed by further extraction of the water layer with ether (2×200 mL) and drying of the combined organic layers with Na2SO4. After removal of the solvent under reduced pressure, the crude material was purified by flash chromatography (EtOAc/hexanes) giving 1.1 g (70%) of [1-(2-trimethylsilanyl-ethoxymethyl)-1H-indol-3yl]-acetic acid methyl ester. 1H NMR (400 MHz, CDCl3): 7.65 (d, J=7.8 Hz, 1H), 7.46 (d, J=8.1, 1H), 7.26 (m, 1H), 7.22 (m, 2H), 5.51 (s, 2H), 3.83 (s, 2H), 3.76 (s, 3H), 3.53 (t, J=7.9 Hz, 2H), 0.94 (t, J=7.9 Hz, 2H), 0.0 (s, 9H).

Workup

  1. waitat rt for 1 h
  2. additionwas added neat
  3. stirringThe reaction mixture was stirred at 0° C. for 15 min
  4. waitat rt for 1 h
  5. customThe reaction mixture was then partitioned between water (200 mL) and diethyl ether (200 mL)
  6. extractionfollowed by further extraction of the water layer with ether (2×200 mL)
  7. dry with materialdrying of the combined organic layers with Na2SO4
  8. customAfter removal of the solvent under reduced pressure
  9. customthe crude material was purified by flash chromatography (EtOAc/hexanes)

Sources & evidence

ORD record
ord-5945098b60b045ed95d6e51fb42f1966
Source dataset
uspto-grants-2008_12
Patent number
US07465808B2

Reaction notes

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