Water → Ethyl 4-cyano-1H-indole-2-carboxylate

HRID 62650Notes

Reaction equation

HRID 62650 reaction equation
Br[C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[NH:6]2.O.[CH3:17][N:18](C=O)C>>[C:17]([C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[NH:6]2)#[N:18]

Participants

4

Reactant 3

HCID 962WaterHCID 6228DimethylformamideHCID 10989255Ethyl 4-bromo-1H-indole-2-carboxylate

Product 1

HCID 53419488Ethyl 4-cyano-1H-indole-2-carboxylateYield 82%

Conditions

Temperature
150 °C

Procedure

To a stirred solution of ethyl 4-bromo-1H-indole-2-carboxylate (500 mg, 1.86 mmol) in DMF (10 mL) was added Cu(I)CN (501 mg, 5.59 mmol) and heated to 150° C. for 24 h. The reaction mixture was cooled to room temperature, the water (25 mL) was added and the reaction mixture extracted with ethyl acetate (4×50 mL). The organic layer was washed with water (25 mL), brine (25 mL), dried over anhydrous Na2SO4 and evaporated under reduced pressure to get the crude product. The crude product was purified by column chromatography over silica gel (100-200 mesh) using a solvent gradient of 10% ethyl acetate in petroleum ether to afford 330 mg (82%) of ethyl 4-cyano-1H-indole-2-carboxylate (I-3a) as an off-white solid.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionthe reaction mixture extracted with ethyl acetate (4×50 mL)
  3. washThe organic layer was washed with water (25 mL), brine (25 mL)
  4. dry with materialdried over anhydrous Na2SO4
  5. customevaporated under reduced pressure
  6. customto get the crude product
  7. customThe crude product was purified by column chromatography over silica gel (100-200 mesh)

Sources & evidence

ORD record
ord-fe4c8cac623845d0b661876aba5915d8
Source dataset
uspto-grants-2016_09
Patent number
US09447039B2

Reaction notes

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