Potassium Carbonate → diethyl 1-(1-cyanoethyl)-1H-indole-2,6-dicarboxylate

HRID 1748243Notes

Reaction equation

HRID 1748243 reaction equation
C([O-])([O-])=O.[K+].[K+].[NH:7]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH:14]=2)[CH:9]=[C:8]1[C:21]([O:23][CH2:24][CH3:25])=[O:22].Br[CH:27]([CH3:30])[C:28]#[N:29]>CN(C=O)C>[C:28]([CH:27]([N:7]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH:14]=2)[CH:9]=[C:8]1[C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH3:30])#[N:29]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 1405382-BromopropionitrileHCID 44754779Diethyl 1H-indole-2,6-dicarboxylate2×

Product 1

HCID 67235490diethyl 1-(1-cyanoethyl)-1H-indole-2,6-dicarboxylateYield 91.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A mixture of K2CO3 (7.9 g, 57.4 mmol) and diethyl 1H-indole-2,6-dicarboxylate (Intermediate A, 5.0 g, 19.1 mmol) in DMF (30 mL) is stirred at room temperature for 30 min. A solution of 2-bromo-propionitrile (3.4 mL, 38.3 mmol) in DMF (10 mL) is added. The reaction mixture is warmed to 80° C. for 6 h and then cooled to room temperature and stirred for another 16 h. Solvent is removed and the residue is partitioned between EtOAc and water. The organic layer is separated, dried and concentrated to afford crude compound which is purified by flash column chromatography using EtOAc in hexanes followed by trituration with acetonitrile to afford the title compound (5.5 g, 91%).

Workup

  1. temperatureThe reaction mixture is warmed to 80° C. for 6 h
  2. temperaturecooled to room temperature
  3. stirringstirred for another 16 h
  4. customSolvent is removed
  5. customthe residue is partitioned between EtOAc and water
  6. customThe organic layer is separated
  7. customdried
  8. concentrationconcentrated
  9. customto afford crude compound which
  10. customis purified by flash column chromatography

Sources & evidence

ORD record
ord-b6d32dc7d089434fa5e652930a62abb3
Source dataset
uspto-grants-2015_10
Patent number
US09150577B2

Reaction notes

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