Dimethylformamide → 5-chloro-1H-indole-3-carbaldehyde

HRID 2303947Notes

Reaction equation

HRID 2303947 reaction equation
P(Cl)(Cl)(Cl)=O.[Cl:6][C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[NH:12][CH:11]=[CH:10]2.[OH-].[Na+].CN(C)[CH:20]=[O:21]>O>[Cl:6][C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[NH:12][CH:11]=[C:10]2[CH:20]=[O:21]

Participants

6

Reactant 4

HCID 6228Dimethylformamide2×HCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 871105-Chloroindole

Product 1

HCID 27953745-chloro-1H-indole-3-carbaldehydeYield 59%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
40 °C

Procedure

To stirred dimethylformamide (20 mL) at 0° C. was added dropwise phosphorus oxychloride (4.6 mL, 49 mmol). The mixture was stirred for 10 min and a solution of 5-chloroindole (5.0 g, 33 mmol) in dimethylformamide (5 mL) was added dropwise. The mixture was heated to 40° C. for 45 min, cooled to room temperature and then treated with a solution of sodium hydroxide (5.9 g, 148 mmol) in water (20 mL). The mixture was heated to 50° C. for 10 min, cooled to room temperature, poured onto crushed ice (100 mL) and filtered. The filter cake was recrystallised (methanol) to give the product as a white solid (3.5 g, 59%): mp 215-216° C.; Found: C, 60.13; H, 3.40; N, 7.75%. C9H6ClNO requires: C, 60.19; H, 3.37; N, 7.79%.

Workup

  1. temperaturecooled to room temperature
  2. temperatureThe mixture was heated to 50° C. for 10 min
  3. temperaturecooled to room temperature
  4. additionpoured
  5. filtrationfiltered
  6. customThe filter cake was recrystallised (methanol)

Sources & evidence

ORD record
ord-9fc6d952156241a1988695d51c1d9b14
Source dataset
uspto-grants-2002_08
Patent number
US06433175B1

Reaction notes

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