Cesium carbonate → 1-(Cyanomethyl)-2-propyl-4-(trifluoromethyl)-1H-indole-5-carbonitrile

HRID 2102091Notes

Reaction equation

HRID 2102091 reaction equation
[CH2:1]([C:4]1[NH:5][C:6]2[C:11]([CH:12]=1)=[C:10]([C:13]([F:16])([F:15])[F:14])[C:9]([C:17]#[N:18])=[CH:8][CH:7]=2)[CH2:2][CH3:3].C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:26][C:27]#[N:28]>C(#N)C>[C:27]([CH2:26][N:5]1[C:6]2[C:11](=[C:10]([C:13]([F:15])([F:16])[F:14])[C:9]([C:17]#[N:18])=[CH:8][CH:7]=2)[CH:12]=[C:4]1[CH2:1][CH2:2][CH3:3])#[N:28]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 11534BromoacetonitrileHCID 674051552-propyl-4-(trifluoromethyl)-1H-indole-5-carbonitrile

Product 1

HCID 578005151-(Cyanomethyl)-2-propyl-4-(trifluoromethyl)-1H-indole-5-carbonitrileYield 95.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 2-propyl-4-(trifluoromethyl)-1H-indole-5-carbonitrile (Example 153A) (1.00 g, 3.96 mmol) in anhydrous acetonitrile (55 mL) was added Cs2CO3 (6.5 g, 20.0 mmol) and bromoacetonitrile (0.713 g, 5.95 mmol). The mixture was heated under N2, for 2 h. Upon cooling, the mixture was partitioned between EtOAc and water. The organic phase was separated, dried (MgSO4) and concentrated in vacuo. The residue was purified by flash chromatography (0-20% EtOAc-hexanes gradient) to afford a pure product (1.1 g, 92% yield): MS (ES) m/z 292 (M+1).

Workup

  1. temperatureThe mixture was heated under N2, for 2 h
  2. temperatureUpon cooling
  3. customthe mixture was partitioned between EtOAc and water
  4. customThe organic phase was separated
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography (0-20% EtOAc-hexanes gradient)

Sources & evidence

ORD record
ord-8f4e21de84874c7180de18ca3325d094
Source dataset
uspto-grants-2009_08
Patent number
US07572820B2

Reaction notes

Loading…