Sodium hydride → 5-methoxy-1-(triisopropylsilyl)-1H-pyrrolo[3,2-b]pyridine

HRID 2378970Notes

Reaction equation

HRID 2378970 reaction equation
[CH3:1][O:2][C:3]1[N:8]=[C:7]2[CH:9]=[CH:10][NH:11][C:6]2=[CH:5][CH:4]=1.[H-].[Na+].[CH3:14][CH:15]([Si:17](Cl)([CH:21]([CH3:23])[CH3:22])[CH:18]([CH3:20])[CH3:19])[CH3:16]>C1COCC1>[CH3:1][O:2][C:3]1[N:8]=[C:7]2[CH:9]=[CH:10][N:11]([Si:17]([CH:21]([CH3:23])[CH3:22])([CH:18]([CH3:20])[CH3:19])[CH:15]([CH3:16])[CH3:14])[C:6]2=[CH:5][CH:4]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 139400Triisopropylsilyl chlorideHCID 53243695-methoxy-1H-pyrrolo[3,2-b]pyridine

Product 1

HCID 590063875-methoxy-1-(triisopropylsilyl)-1H-pyrrolo[3,2-b]pyridineYield 100.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-methoxy-1H-pyrrolo[3,2-b]pyridine (4.0 g, 27.0 mmol) in THF (50 mL) was added NaH (60%, 1.30 g, 32.4 mmol) in small portions at 0° C. over 10 min. The resulting mixture was stirred under N2 for 1 hr, followed by dropwise addition of TIPS-Cl (6.86 mL, 32.4 mmol) in neat through an syringe at 0° C. over 2 min, and stirred for additional 1 hr. The reaction was quenched with sat. NH4Cl (50 mL), extracted with Et2O (500 mL). The extract was washed with brine (50 mL), dried (MgSO4), concentrated on rotary vacuo, and the residue was purified on Biotage Flash Collector eluting with 20-75% EtOAc/Hexanes (1600 mL) to afford the expected product, 5-methoxy-1-(triisopropylsilyl)-1H-pyrrolo[3,2-b]pyridine (8.25 g, 100%). 1H NMR (400 MHz, CHLOROFORM-D) δ ppm 1.11 (d, J=7.55 Hz, 19 H) 1.57-1.67 (m, J=7.55, 7.55, 7.55, 7.55 Hz, 3 H) 3.98 (s, 3 H) 6.54 (d, J=9.06 Hz, 1 H) 6.67 (d, J=3.02 Hz, 1 H) 7.35 (d, J=3.27 Hz, 1 H) 7.65 (d, J=9.06 Hz, 1 H); Mass spec 305.1 (MH+) calc. for C17H28N2O Si 304.2.

Workup

  1. stirringstirred for additional 1 hr
  2. customThe reaction was quenched with sat. NH4Cl (50 mL)
  3. extractionextracted with Et2O (500 mL)
  4. washThe extract was washed with brine (50 mL)
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated on rotary vacuo
  7. customthe residue was purified on Biotage Flash Collector
  8. washeluting with 20-75% EtOAc/Hexanes (1600 mL)

Sources & evidence

ORD record
ord-96ee4cf0c73a471dbbbb2ab2cb512176
Source dataset
uspto-grants-2008_12
Patent number
US07470680B2

Reaction notes

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