Dimethylformamide → Ethyl 3-chloro-5-cyano-1H-indole-1-propanoate

HRID 423349Notes

Reaction equation

HRID 423349 reaction equation
[Cl:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]#[N:12])[CH:9]=2)[NH:4][CH:3]=1.[CH2:13]([O:15][C:16](=[O:20])[CH2:17][CH2:18]Br)[CH3:14].C(=O)([O-])[O-].[Cs+].[Cs+].CN(C=O)C>C(OCC)C>[Cl:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]#[N:12])[CH:9]=2)[N:4]([CH2:18][CH2:17][C:16]([O:15][CH2:13][CH3:14])=[O:20])[CH:3]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 68320Ethyl 3-bromopropionateHCID 59318394HCID 59318394, compound

Product 1

HCID 59318420Ethyl 3-chloro-5-cyano-1H-indole-1-propanoateYield 90.3%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 3-chloro-1H-indole-5-carbonitrile (D94) (1.8 g, 10 mmol), ethyl-3-bromopropionate (1.92 ml, 15 mmol), cesium carbonate (6.5 g, 20 mmol) and DMF (50 ml) was heated at 80° C. for 4 hours to give complete reaction. After allowing mixture to cool to room temperature diethyl ether (300 ml) was added and the solution washed with water (3×300 ml). Dried over MgSO4 and evaporated off the solvent to give a brown solid. The solid was triturated with a mixture of diethyl ether and hexane to obtain 2.5 g of the title compound as a tan solid. Crude product used in the next stage (synthesis of D96).

Workup

  1. customto give complete
  2. customreaction
  3. additionwas added
  4. washthe solution washed with water (3×300 ml)
  5. dry with materialDried over MgSO4
  6. customevaporated off the solvent
  7. customto give a brown solid
  8. customThe solid was triturated with a mixture of diethyl ether and hexane

Sources & evidence

ORD record
ord-b6d7d17cc8b444279b14682488352b7b
Source dataset
uspto-grants-2012_01
Patent number
US08101775B2

Reaction notes

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