Water → 5-bromo-3-formyl-1H-indole-6-carbonitrile

HRID 1054594Notes

Reaction equation

HRID 1054594 reaction equation
P(Cl)(Cl)(Cl)=O.[Br:6][C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][C:15]=1[C:16]#[N:17])[NH:12][CH:11]=[CH:10]2.O.[OH-].[Na+].CN([CH:24]=[O:25])C>>[Br:6][C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][C:15]=1[C:16]#[N:17])[NH:12][CH:11]=[C:10]2[CH:24]=[O:25]

Participants

6

Reactant 5

HCID 962WaterHCID 6228Dimethylformamide2×HCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 866985975-bromo-1H-indole-6-carbonitrile

Product 1

HCID 866985965-bromo-3-formyl-1H-indole-6-carbonitrileYield 92%

Conditions

Temperature
80 °C

Procedure

Phosphorus oxychloride (1.39 mL, 14.9 mmol) was added dropwise over 5 minutes to DMF (10 mL) with stirring. The clear mixture was stirred at room temperature for 10 minutes. A solution of 5-bromo-1H-indole-6-carbonitrile (1.10 g, 4.97 mmol) in DMF (1.5 with 0.5 mL wash) was added to the clear red solution, and the reaction mixture was stirred at room temperature for 5 min. The resulting grey suspension was heated to 80° C. under nitrogen for 25 min, and then allowed to cool to room temperature. The reaction mixture was treated slowly with water (30 mL) and aqueous 1 N NaOH (30 mL) at room temperature. The resulting thick suspension was then heated to 85° C. for five minutes with vigorous stirring. The reaction mixture was allowed to cool to room temperature over 5 minutes, and the solids were collected by filtration. The solids were dried in vacuo for 16 hours at 55° C. to afford the title compound (1.15 g, 92%) as a cream-colored solid. MS (ES−) 247.1 (M−H)−. 1H NMR (500 MHz, DMSO-d6) δ 12.76 (br. s., 1H), 9.99 (s, 1H), 8.60 (s, 1H), 8.43 (s, 1H), 8.18 (s, 1H).

Workup

  1. stirringThe clear mixture was stirred at room temperature for 10 minutes
  2. stirringthe reaction mixture was stirred at room temperature for 5 min
  3. temperatureto cool to room temperature
  4. temperatureThe resulting thick suspension was then heated to 85° C. for five minutes with vigorous stirring
  5. temperatureto cool to room temperature over 5 minutes
  6. filtrationthe solids were collected by filtration
  7. customThe solids were dried in vacuo for 16 hours at 55° C.

Sources & evidence

ORD record
ord-2dc9cdd5c3754ada9d9f32a7732b8b67
Source dataset
uspto-grants-2016_07
Patent number
US09394285B2

Reaction notes

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