Carbon Dioxide → Indole-2-carboxaldehyde

HRID 857162Notes

Reaction equation

HRID 857162 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.C([Li])CCC.[C:15](=O)=[O:16].C([Li])(C)(C)C.CN(C)C=O>C1COCC1.C(OCC)C.O>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[C:2]1[CH:15]=[O:16]

Participants

9

Reactant 5

HCID 280Carbon DioxideHCID 798IndoleHCID 6228DimethylformamideHCID 178418306HCID 178418306, compoundHCID 178418339Butyllithium

Product 1

HCID 96389Indole-2-carboxaldehydeYield 58%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

Indole (74) (1.00 g, 8.54 mmol) was dissolved in 50 mL of dry THF. The resulting solution was cooled at −78° C. A solution of 2.5 M of n-butyllithium (3.80 mL, 9.39 mmol) was slowly added to the THF solution and was stirred for 30 min. Carbon dioxide was passed through the reaction mixture over 10 min. The resulting solution was allowed to warm to room temperature. The excess of carbon dioxide was removed under reduced pressure while the solution was concentrated to 25 mL. 50 mL of dry THF was added to the concentrated solution, which was cooled again to −78° C. A solution of 1.7 M of tert-butyllithium (5.00 mL, 8.54 mmol) was slowly added to the THF solution, which was stirred at −78° C. for 1 hour. Anhydrous N,N-dimethylformamide (0.83 mL, 8.5 mmol) was added to the solution. The resulting mixture was warmed to room temperature over a period of 1.5 hours. Water (10 mL) was added and the mixture was stirred for 15 min. Diethyl ether was added. The organic layer was washed with brine (3×). The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. The solid was purified over silica gel using 80/20 hexanes/ethyl acetate as eluent to give Compound 75, (0.7129 g, 58%). 1H NMR (500 MHz, CDCl3): d (ppm), 9.88 (s, 1H); 7.77 (d, 1H, J=8.1 Hz); 7.48 (d, 1H, J=8.3 Hz); 7.41 (t, 1H, J=7.0 Hz); 7.3 (s, 1H); 7.20 (t, 1H, J=7.4 Hz). 13C NMR (500 MHz, CDCl3): δ (ppm), 182.89; 138.80; 136.87; 128.25; 124.37; 122.20; 115.60; 113.28.

Workup

  1. temperatureto warm to room temperature
  2. customThe excess of carbon dioxide was removed under reduced pressure while the solution
  3. concentrationwas concentrated to 25 mL
  4. addition50 mL of dry THF was added to the concentrated solution, which
  5. temperaturewas cooled again to −78° C
  6. stirringwas stirred at −78° C. for 1 hour
  7. temperatureThe resulting mixture was warmed to room temperature over a period of 1.5 hours
  8. stirringthe mixture was stirred for 15 min
  9. washThe organic layer was washed with brine (3×)
  10. dry with materialThe organic layer was dried over magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customThe solid was purified over silica gel using 80/20 hexanes/ethyl acetate as eluent

Sources & evidence

ORD record
ord-9198b21aa64542e08e59a17b358f44e1
Source dataset
uspto-grants-2006_12
Patent number
US07144912B2

Reaction notes

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