Water → 3-Cyano-5-methoxy-2-(trifluoromethyl)indole

HRID 1449631Notes

Reaction equation

HRID 1449631 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7]([C:12]([F:15])([F:14])[F:13])=[CH:6]2.ClS([N:20]=[C:21]=O)(=O)=O.CN(C)C=O.O>C(#N)C>[C:21]([C:6]1[C:5]2[C:9](=[CH:10][CH:11]=[C:3]([O:2][CH3:1])[CH:4]=2)[NH:8][C:7]=1[C:12]([F:15])([F:13])[F:14])#[N:20]

Participants

6

Reactant 4

HCID 962WaterHCID 6228DimethylformamideHCID 70918Chlorosulfonyl isocyanateHCID 153353435-Methoxy-2-(trifluoromethyl)-1H-indole

Product 1

HCID 153353443-Cyano-5-methoxy-2-(trifluoromethyl)indoleYield 25%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 5-methoxy-2-(trifluoromethyl)indole (3.0 g, 13.0 mmole) in acetonitrile is treated dropwise with chlorosulfonyl isocyanate (2.02 g, 14.3 mmole) at 0° C., stirred at ambient temperatures for 2.5 hours, treated with dimethylformamide (DMF) (2.1 g, 28.6 mmole), stirred at ambient temperatures for 0.75 hour and poured into water. The resultant mixture is extracted with diethyl ether. The combined extracts are washed sequentially with water and brine, dried over MgSO4 and concentrate in vacuo to give a brown oil residue. The oil is crystallized in ether/hexanes to give the title product as brown crystals, 0.78 g (25% yield), mp 189°-190° C., identified by IR, 1HNMR, 13CNMR and 19FNMR.

Workup

  1. stirringstirred at ambient temperatures for 0.75 hour
  2. extractionThe resultant mixture is extracted with diethyl ether
  3. washThe combined extracts are washed sequentially with water and brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrate in vacuo
  6. customto give a brown oil residue
  7. customThe oil is crystallized in ether/hexanes

Sources & evidence

ORD record
ord-7f48494cadb8424aa2e18f8ddf2adcc3
Source dataset
uspto-grants-1997_02
Patent number
US05599832

Reaction notes

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