Triethylamine → 1H,2H,3H-pyrrolo(2,3-b)pyridine

HRID 1515596Notes

Reaction equation

HRID 1515596 reaction equation
C(N(CC)CC)C.[NH:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][N:15]=2)[CH:10]=[CH:9]1>[Pd].C(O)=O>[NH:8]1[C:16]2=[N:15][CH:14]=[CH:13][CH:12]=[C:11]2[CH2:10][CH2:9]1

Participants

5

Reactant 2

HCID 8471TriethylamineHCID 92221H-Pyrrolo(2,3-b)pyridine

Product 1

HCID 100118891H,2H,3H-pyrrolo(2,3-b)pyridineYield 61.4%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 284Formic AcidSolvent2×

Conditions

Temperature
80 °C

Procedure

Formic acid (98%, 37.5 mL, 0.97 mol) was added to cooled (ice bath) triethylamine (150 mL, 1.08 mol) and stirred for 20 min. The resulting two-phase system was added to a mixture of 7-azaindole (50.0 g, 0.42 mol), formic acid (750 mL), and 10% palladium on activated carbon (30.0 g) at 0° C. and the resulting mixture was then heated at 80° C. for 5 days. The mixture was then cooled to room temperature, the catalyst was removed by filtration and washed with formic acid. The filtrate and washings were combined and concentrated in vacuo. The residual liquid was cooled (ice bath) and basified to pH=13 by slow addition of a 50% aqueous solution of sodium hydroxide. The resulting solution was refluxed for 1 h and then cooled to room temperature. The precipitate formed was filtered and washed with hexane to give 2,3-dihydro-1H-pyrrolo[2,3-b]pyridine (31 g) as a light yellow solid. The filtrate was then extracted with ethyl acetate, washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. Purification by flash silica gel chromatography (silica gel from QingDao, 200-300 mesh, glass column from Shanghai SD company, hexanes) afforded another batch of 2,3-dihydro-1H-pyrrolo[2,3-b]pyridine (9.5 g) as a light yellow solid (total yield 40.5 g, 81%): 1H NMR (400 MHz, CDCl3) δ ppm 3.06 (t, J=8.3 Hz, 2H), 3.61 (t, J=8.3 Hz, 2H), 4.50 (br, 1H), 6.50 (m, 1H), 7.24 (m, 1H), 7.81 (d, J=5.2 Hz, 1H).

Workup

  1. temperatureThe mixture was then cooled to room temperature
  2. customthe catalyst was removed by filtration
  3. washwashed with formic acid
  4. concentrationconcentrated in vacuo
  5. temperatureThe residual liquid was cooled (ice bath)
  6. additionbasified to pH=13 by slow addition of a 50% aqueous solution of sodium hydroxide
  7. temperatureThe resulting solution was refluxed for 1 h
  8. temperaturecooled to room temperature
  9. customThe precipitate formed
  10. filtrationwas filtered
  11. washwashed with hexane

Sources & evidence

ORD record
ord-552c16549bd74367becb97467ec500af
Source dataset
uspto-grants-2012_07
Patent number
US08222416B2

Reaction notes

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