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

HRID 1710448Notes

Reaction equation

HRID 1710448 reaction equation
C([O-])([O-])=O.[K+].[K+].[CH2:7]([O:9][C:10]([C:12]1[NH:13][C:14]2[C:19]([CH:20]=1)=[CH:18][CH:17]=[C:16]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH:15]=2)=[O:11])[CH3:8].Br[CH:27]([CH3:30])[C:28]#[N:29]>CN(C=O)C>[CH2:7]([O:9][C:10]([C:12]1[N:13]([CH:27]([C:28]#[N:29])[CH3:30])[C:14]2[C:19]([CH:20]=1)=[CH:18][CH:17]=[C:16]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH:15]=2)=[O:11])[CH3:8]

Participants

5

Reactant 3

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

Product 1

HCID 67235490diethyl 1-(1-cyanoethyl)-1H-indole-2,6-dicarboxylateYield 64.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A mixture of K2CO3 (7.93 g, 57.0 mmol) and 1H-indole-2,6-dicarboxylic acid diethyl ester (5.0 g, 19.14 mmol) in DMF (30 mL) was stirred at room temperature for 0.5 h. Then 2-bromo-propionitrile (3.4 mL, 38.3 mmol) in DMF (10 mL) was added. The reaction was warmed to 80° C. and kept at this temperature for 6 h. Then the reaction was cooled down to the room temperature. Most of the DMF solvent was removed in vacuo and the crude residue was extracted several times with EtOAc. The combined organic extracts were washed with brine, dried over MgSO4 and concentrated. The crude product was triturated with MeCN to give 3.9 g of 1-(cyano-methyl-methyl)-1H-indole-2,6-dicarboxylic acid diethyl ester as a white fluffy solid. The filtrate was concentrated and purification by silica gel chromatography provided 1.6 g of 1-(cyano-methyl-methyl)-1H-indole-2,6-dicarboxylic acid diethyl ester, yield 91%.

Workup

  1. temperatureThe reaction was warmed to 80° C.
  2. waitkept at this temperature for 6 h
  3. temperatureThen the reaction was cooled down to the room temperature
  4. customMost of the DMF solvent was removed in vacuo
  5. extractionthe crude residue was extracted several times with EtOAc
  6. washThe combined organic extracts were washed with brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated
  9. customThe crude product was triturated with MeCN

Sources & evidence

ORD record
ord-7abc3b1c62764aa3a202a7144780f25c
Source dataset
uspto-grants-2010_09
Patent number
US07790712B2

Reaction notes

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