Dimethylformamide → 2-(pyridin-3-yl)-1H-indole-3-carbaldehyde

HRID 1980879Notes

Reaction equation

HRID 1980879 reaction equation
P(Cl)(Cl)(Cl)=O.[N:6]1[CH:11]=[CH:10][CH:9]=[C:8]([C:12]2[NH:13][C:14]3[C:19]([CH:20]=2)=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH:7]=1.CN(C)[CH:23]=[O:24]>>[N:6]1[CH:11]=[CH:10][CH:9]=[C:8]([C:12]2[NH:13][C:14]3[C:19]([C:20]=2[CH:23]=[O:24])=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH:7]=1

Participants

4

Reactant 3

HCID 6228Dimethylformamide2×HCID 24813Phosphorus oxychlorideHCID 6066772-(pyridin-3-yl)-1H-indole

Product 1

HCID 27717142-(pyridin-3-yl)-1H-indole-3-carbaldehyde

Procedure

Phosphorus oxychloride (3.36 ml) is added dropwise over a period of 20 minutes to dimethylformamide (10.6 g) maintained at 0°-3°. After complete addition a solution of 2-(3-pyridyl)indole (6.50 g) in dimethylformamide (20 ml) is added dropwise over a period of 30 minutes at such a rate so that the reaction temperature does not exceed 10°. The cooling bath is then removed and the viscous solution heated to and maintained at 35°-40° for 1 hour. The reaction mixture is treated with crushed ice (50 g). A solution of sodium hydroxide (24.4 g) in 65 ml of water is added slowly. After the addition the resulting red-orange solution is heated rapidly to reflux and maintained at reflux for about 2 minutes. The solution is allowed to cool to room temperature, then placed in a freezer for 2 days. The resulting precipitate is collected and washed well with water to give an orange solid which is recrystallized from methanol (240 ml) to give 2-(3pyridyl)-indole-3-carboxaldehyde, m.p. 236°-238°.

Workup

  1. temperaturemaintained at 0°-3°
  2. additionis added dropwise over a period of 30 minutes at such a rate so that the reaction temperature
  3. customdoes not exceed 10°
  4. customThe cooling bath is then removed
  5. temperaturethe viscous solution heated to and
  6. temperaturemaintained at 35°-40° for 1 hour
  7. additionThe reaction mixture is treated with crushed ice (50 g)
  8. additionA solution of sodium hydroxide (24.4 g) in 65 ml of water is added slowly
  9. additionAfter the addition the resulting red-orange solution
  10. temperatureis heated rapidly
  11. temperatureto reflux
  12. temperaturemaintained
  13. temperatureat reflux for about 2 minutes
  14. customThe resulting precipitate is collected
  15. washwashed well with water
  16. customto give an orange solid which
  17. customis recrystallized from methanol (240 ml)

Sources & evidence

ORD record
ord-202a25ab0813481198e051c92f901e8f
Source dataset
uspto-grants-1985_04
Patent number
US04511573

Reaction notes

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