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

HRID 338251Notes

Reaction equation

HRID 338251 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 1N 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-e25d737fe7f94bdfa40d8458ae76f7c8
Source dataset
uspto-grants-2014_11
Patent number
US08889730B2

Reaction notes

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