Sodium hydride → 5-bromo-3-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridine

HRID 2234656Notes

Reaction equation

HRID 2234656 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:10]([I:11])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[H-].[Na+].[CH3:14][Si:15]([CH3:22])([CH3:21])[CH2:16][CH2:17][O:18][CH2:19]Cl.[Cl-].[NH4+]>CO.O1CCCC1>[Br:1][C:2]1[CH:3]=[C:4]2[C:10]([I:11])=[CH:9][N:8]([CH2:19][O:18][CH2:17][CH2:16][Si:15]([CH3:22])([CH3:21])[CH3:14])[C:5]2=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 242292125-Bromo-3-iodo-1H-pyrrolo(2,3-b)pyridine

Product 1

HCID 592970265-bromo-3-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridineYield 90.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Into a 50 ml round bottom flask were added 5-bromo-3-iodo-1H-pyrrolo[2,3-b]pyridine (1.86 g, 5.78 mmol) and dry tetrahydrofuran (20 ml). The solution was cooled in an ice bath at 0° C. and sodium hydride (305 mg, 60% dispersion in mineral oil, 6.36 mmol) was added in small portions. After 20 minutes, 2-(trimethylsilyl)ethoxymethyl chloride (1.12 mL, 6.35 mmol) was added, and the reaction mixture was allowed to warm to room temperature over 30 minutes. The reaction mixture was allowed stirred at this temperature for an additional 30 minutes. Methanol (1.0 mL) was then added to quench the reaction, followed by the addition of saturated aqueous ammonium chloride solution (10 mL). The mixture was then extracted with dichloromethane (2×20 mL). The organic layers were combined, dried over sodium sulfate, filtered, and concentrated. The residue was purified by flash chromatography (20% ethyl acetate in hexanes) to give 2.36 g (90%) 5-bromo-3-iodo-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridine as a yellowish oil. 1H-NMR (250 MHz, CDCl3) δ 8.49 (d, J=2 Hz, 1H), 7.84 (d, J=2.25 Hz, 1H), 7.44 (s, 1H), 3.50 (t, J=8.25 Hz, 2H), 0.88 (t, J=8.25 Hz, 2H), −0.08 (s, 9H); MS: m/z 452.9+454.9 (M+H+).

Workup

  1. temperatureto warm to room temperature over 30 minutes
  2. customto quench
  3. customthe reaction
  4. extractionThe mixture was then extracted with dichloromethane (2×20 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by flash chromatography (20% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-31447d5cb2c047a38b8257990d91f071
Source dataset
uspto-grants-2010_05
Patent number
US07709645B2

Reaction notes

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