Sodium hydride → 1-(tert-Butyl-dimethyl-silanyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine

HRID 1515597Notes

Reaction equation

HRID 1515597 reaction equation
[NH:1]1[C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[CH2:3][CH2:2]1.[H-].[Na+].[Si:12](Cl)([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13]>CN(C)C=O>[C:15]([Si:12]([CH3:14])([CH3:13])[N:1]1[C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[CH2:3][CH2:2]1)([CH3:18])([CH3:17])[CH3:16]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 28928tert-Butyldimethylsilyl chlorideHCID 100118891H,2H,3H-pyrrolo(2,3-b)pyridine

Product 1

HCID 587309361-(tert-Butyl-dimethyl-silanyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridineYield 66.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

To a 0° C. solution of 2,3-dihydro-1H-pyrrolo[2,3-b]pyridine (24.0 g, 200 mmol) in N,N-dimethylformamide (68 mL) was added a 60% dispersion of sodium hydride in mineral oil (12.0 g, 300 mmol) portionwise. The mixture was stirred at 0° C. for 30 min and then a solution of tert-butyldimethylsilyl chloride (46 g, 300 mmol) in N,N-dimethylformamide (100 mL) was added to the above mixture dropwise at 0° C. The mixture was stirred at 0° C. for 3 h and then extracted with ethyl acetate, washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The yellowish residue was purified by flash silica gel chromatography (silica gel from QingDao, 200-300 mesh, glass column from Shanghai SD company, 5% ethyl acetate/hexanes) to afford 1-(tert-butyl-dimethyl-silanyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine (31 g, 66%) as a yellow oil: LC/MS m/e calcd for C13H23N2Si [M+H]+ 235.42, observed 235.3; 1H NMR (400 MHz, CDCl3) δ ppm 0.35 (s, 6H), 0.98 (s, 9H, 3×CH3), 3.02 (t, J=8.6 Hz, 2H), 3.68 (t, J=8.6 Hz, 2H), 6.40 (dd, J=5.2 Hz, 7.0 Hz, 1H), 7.15 (d, J=7.0 Hz, 1H), 7.80 (d, J=5.2 Hz, 1H).

Workup

  1. stirringThe mixture was stirred at 0° C. for 3 h
  2. extractionextracted with ethyl acetate
  3. washwashed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe yellowish residue was purified by flash silica gel chromatography (silica gel from QingDao, 200-300 mesh, glass column from Shanghai SD company, 5% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-0c734f72d90344e388b0239e8b5c2221
Source dataset
uspto-grants-2012_07
Patent number
US08222416B2

Reaction notes

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