2-Chloromethyl 2-(trimethylsilyl)ethyl ether → 7-Bromo-1-(2-trimethylsilanyl-ethoxymethyl)-1H-indole

HRID 2215760Notes

Reaction equation

HRID 2215760 reaction equation
[CH3:1][Si:2]([CH2:5][CH2:6][O:7][CH2:8]Cl)([CH3:4])[CH3:3].[Br:10][C:11]1[CH:12]=[CH:13][CH:14]=[C:15]2[C:19]=1[NH:18][CH:17]=[CH:16]2>CN(C=O)C>[Br:10][C:11]1[CH:12]=[CH:13][CH:14]=[C:15]2[C:19]=1[N:18]([CH2:8][O:7][CH2:6][CH2:5][Si:2]([CH3:4])([CH3:3])[CH3:1])[CH:17]=[CH:16]2

Participants

4

Reactant 2

HCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 27570207-Bromoindole

Product 1

HCID 219500727-Bromo-1-(2-trimethylsilanyl-ethoxymethyl)-1H-indoleYield 79%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride in mineral oil (60% by wt., 0.62 g; 15.5 mmol) was washed with hexanes and suspended in DMF (40 mL). SEM-Cl (2.0 mL, 11.3 mmol) was added followed by a solution of 7-bromoindole in DMF (15 mL) dropwise over 5 min. The resultant white suspension was stirred overnight at room temperature and then the reaction was quenched with saturated aqueous NaHCO3. The mixture was poured into EtOAc and the organic layer was separated and washed with pH 7 buffer, saturated aqueous NaHCO3, brine dried (MgSO4) and concentrated to a light yellow oil. Flash chromatography (2 to 5% EtOAc/hexanes) afforded the title compound as a colorless oil (2.58 g, 79%). 1H NMR (400 MHz, DMSO-d6) 7.58–7.61 (m, 2H), 7.36 (d, J=8 Hz, 1H), 6.70 (dd, J=8, 8 Hz, 1H), 6.55 (d, J=3 Hz, 1H), 5.80 (2, 2H), 3.45 (t, J=8 Hz, 2H), 0.80 (t, J=8 Hz, 2H), 0.01 (s, 9H). 13C NMR (75.7 MHz, DMSO-d6) 132.58, 132.31, 131.92, 126.69, 121.19, 120.26, 103.50, 102.03, 75.69, 64.45, 17.18, −1.46. MS (FD+, m/z) 327, 325 (M+). HRMS 326.0570 (M++1, calcd for C14H21NOSiBr 326.0576).

Workup

  1. washSodium hydride in mineral oil (60% by wt., 0.62 g; 15.5 mmol) was washed with hexanes
  2. customthe reaction was quenched with saturated aqueous NaHCO3
  3. additionThe mixture was poured into EtOAc
  4. customthe organic layer was separated
  5. washwashed with pH 7 buffer
  6. dry with materialsaturated aqueous NaHCO3, brine dried (MgSO4)
  7. concentrationconcentrated to a light yellow oil

Sources & evidence

ORD record
ord-a781787dbdc24bb3b6ad9763e0f006af
Source dataset
uspto-grants-2006_09
Patent number
US07109229B2

Reaction notes

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