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

HRID 1994183Notes

Reaction equation

HRID 1994183 reaction equation
CCN(CC)CC.[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)pyridine

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 284Formic AcidSolvent2×

Procedure

98% Formic acid (37.5 mL, 0.97 mol) was added to a stirred and cooled (ice bath) neat Et3N (150 mL, 1.08 mol). A two-phase system, which was formed, was then added to a mixture of 7-azaindole (50.0 g, 0.424 mol), formic acid (750 mL), and 10% palladium on activated carbon (26.75 g, Degussa type), and stirred at 80° C. for 4 d. The mixture was cooled to r.t., the catalyst was filtered off and washed with formic acid (100 mL). The filtrate and washings were combined and concentrated in vacuum. The residual liquid was cooled (ice bath) and basified to pH 13 by slow addition of 50% aqueous NaOH (total of about 500 mL). Then, the mixture was refluxed for 2 h until TLC showed completion. Ice was added in amount sufficient to lower the temperature of the mixture to 20° C. The two-phase system was then extracted with AcOEt (5×500 mL). Combined extracts were washed with brine, dried MgSO4, and concentrated in vacuum. The residual brown solid was separated by means of SGC with AcOEt:MeOH as eluent to afford recovered 1 (12.57 g, 25%) and desired 2 (36.05 g, 71%). 1H NMR (400 MHz, CDCl3) δ 3.05 (t, J=8.4 Hz, 2H), 3.60 (t, J=8.4 Hz, 2H), 4.52 (bs, 1H), 6.49 (dd, J=7.0, 5.3 Hz, 1H), 7.23 (dq, J=7.0, 1.3 Hz, 1H), 7.81 (ddt, J=5.3, 1.3, 1.1 Hz, 1H).

Workup

  1. customA two-phase system, which was formed
  2. stirringstirred at 80° C. for 4 d
  3. filtrationthe catalyst was filtered off
  4. washwashed with formic acid (100 mL)
  5. concentrationconcentrated in vacuum
  6. temperatureThe residual liquid was cooled (ice bath)
  7. additionbasified to pH 13 by slow addition of 50% aqueous NaOH (total of about 500 mL)
  8. temperatureThen, the mixture was refluxed for 2 h until TLC
  9. additionIce was added in amount sufficient
  10. customto 20° C
  11. extractionThe two-phase system was then extracted with AcOEt (5×500 mL)
  12. washCombined extracts were washed with brine, dried MgSO4
  13. concentrationconcentrated in vacuum
  14. customThe residual brown solid was separated by means of SGC with AcOEt
  15. customMeOH as eluent to afford
  16. customrecovered 1 (12.57 g, 25%)

Sources & evidence

ORD record
ord-993195e0982e48e29bb8a3e7ef6c8a7a
Source dataset
uspto-grants-2010_01
Patent number
US07652137B2

Reaction notes

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