4-Toluenesulfonyl chloride → 1-tosyl-1H-indole-6-carbonitrile

HRID 475178Notes

Reaction equation

HRID 475178 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:10]#[N:11])[CH:8]=2)[CH:3]=[CH:2]1.[H-].[Na+].[S:14](Cl)([C:17]1[CH:23]=[CH:22][C:20]([CH3:21])=[CH:19][CH:18]=1)(=[O:16])=[O:15]>C1COCC1>[S:14]([N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:10]#[N:11])[CH:8]=2)[CH:3]=[CH:2]1)([C:17]1[CH:23]=[CH:22][C:20]([CH3:21])=[CH:19][CH:18]=1)(=[O:16])=[O:15]

Participants

5

Reactant 3

HCID 73974-Toluenesulfonyl chlorideHCID 24758Sodium hydrideHCID 851461H-indole-6-carbonitrile

Product 1

HCID 712719531-tosyl-1H-indole-6-carbonitrileYield 67.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1H-indole-6-carbonitrile (70 mg, 0.5 mmol, CASRN 15861-36-6) in THF (5 mL) cooled to 0° C. was added with vigorous stirring NaH (25 mg, 60% in oil, 0.65 mmol). After stirring for 30 min, TsCl (140 mg, 0.75 mmol) was added to the mixture. The reaction mixture was stirred at RT for 18 h then partitioned between DCM (300 mL) and water (50 mL). The organic layer was separated, dried (MgSO4), filtered and concentrated in vacuo. The resulting residue was purified by SiO2 chromatography eluting with a petroleum ether/EtOAc gradient (5 to 10% EtOAc) to afford 100 mg (67%) of 1-tosyl-1H-indole-6-carbonitrile (34) as a white solid: MS (ESI) m/z=297.1 [M+1]+.

Workup

  1. additionwas added
  2. stirringThe reaction mixture was stirred at RT for 18 h
  3. customthen partitioned between DCM (300 mL) and water (50 mL)
  4. customThe organic layer was separated
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe resulting residue was purified by SiO2 chromatography
  9. washeluting with a petroleum ether/EtOAc gradient (5 to 10% EtOAc)

Sources & evidence

ORD record
ord-8d3ca324e10943979ed0eb2765541c17
Source dataset
uspto-grants-2014_01
Patent number
US08637537B2

Reaction notes

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