1H-Pyrrolo(2,3-b)pyridine → 1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridine

HRID 1776816Notes

Reaction equation

HRID 1776816 reaction equation
[H-].[Na+].[NH:3]1[C:7]2=[N:8][CH:9]=[CH:10][CH:11]=[C:6]2[CH:5]=[CH:4]1.[CH3:12][Si:13]([CH2:16][CH2:17][O:18][CH2:19]Cl)([CH3:15])[CH3:14]>CN(C=O)C>[CH3:12][Si:13]([CH3:15])([CH3:14])[CH2:16][CH2:17][O:18][CH2:19][N:3]1[C:7]2=[N:8][CH:9]=[CH:10][CH:11]=[C:6]2[CH:5]=[CH:4]1

Participants

5

Reactant 3

HCID 92221H-Pyrrolo(2,3-b)pyridineHCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl ether

Product 1

HCID 584313511-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridineYield 74.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

NaH (4.90 g, 203.2 mmol) was added to a solution of 1H-pyrrolo[2,3-b]pyridine (20.0 g, 169.3 mmol) in dry DMF (200 mL) under N2 protection. The mixture was stirred at 0° C. for 1 hour. Then SEMCl (42.2 g, 253.95 mmol) was added to the reaction mixture, and the mixture was stirred at 0° C. for 4 hours. After concentrated in vacuo to remove DMF, ice cold NH4Cl (sat. aq.) was added and the mixture was extracted with EtOAc. The organic layer was washed with water, brine, dried over Na2SO4, filtered and the solvent was concentrated in vacuo under reduced pressure. The crude product was purified using column chromatography (petroleum ether:EtOAc=10:1) to provide the product of 1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridine (31.2 g, yield: 74%). 1H-NMR (CDCl3, 400 MHz) δ 8.33 (dd, J=4.8 Hz, 1.6 Hz, 1H), 7.91 (dd, J=7.6 Hz, 1.6 Hz, 1H), 7.34 (d, J=3.6 Hz, 1H), 7.08 (dd, J=7.6 Hz, 4.8 Hz, 1H), 6.51 (d, J=3.6 Hz, 1H), 5.68 (s, 2H), 3.53 (t, J=8.4 Hz, 2H), 0.90 (t, J=8.4 Hz, 2H), −0.08 (s, 9H). MS (M+H)+: 249.

Workup

  1. stirringthe mixture was stirred at 0° C. for 4 hours
  2. concentrationAfter concentrated in vacuo
  3. customto remove DMF, ice cold NH4Cl (sat. aq.)
  4. additionwas added
  5. extractionthe mixture was extracted with EtOAc
  6. washThe organic layer was washed with water, brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationthe solvent was concentrated in vacuo under reduced pressure
  10. customThe crude product was purified

Sources & evidence

ORD record
ord-b72bb5d4e98a498f85f177a15b819f86
Source dataset
uspto-grants-2016_02
Patent number
US09265773B2

Reaction notes

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