Acetonitrile → 3-(1-benzenesulfonyl-1H-indol-2-yl)-3-oxo-propionitrile

HRID 74444Notes

Reaction equation

HRID 74444 reaction equation
[C:1](#[N:3])[CH3:2].C(O[C:7]([C:9]1[N:10]([S:18]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)(=[O:20])=[O:19])[C:11]2[C:16]([CH:17]=1)=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:8])C.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[Cl-].[NH4+]>O.O1CCCC1>[C:21]1([S:18]([N:10]2[C:11]3[C:16](=[CH:15][CH:14]=[CH:13][CH:12]=3)[CH:17]=[C:9]2[C:7](=[O:8])[CH2:2][C:1]#[N:3])(=[O:19])=[O:20])[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 25517Ammonium ChlorideHCID 506886Ethyl 1-(benzenesulfonyl)indole-2-carboxylateHCID 2733832Lithium Hexamethyldisilazide

Product 1

HCID 680047663-(1-benzenesulfonyl-1H-indol-2-yl)-3-oxo-propionitrileYield 144.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

Acetonitrile (10.6 g, 0.202 mol) was added to a tetrahydrofuran (THF) solution (135 ml) of 1-benzenesulfonyl-1H-indole-2-carboxylic acid ethyl ester (33.4 g, 0.101 mol), and cooled to −78° C. A tetrahydrofuran (THF) solution of 1 M lithium bis(trimethylsilyl) amide (213 ml, 0.213 mol) was added dropwise thereto, and stirred for 30 minutes. A saturated aqueous solution (83 ml) of ammonium chloride was added to the reaction mixture, and stirred for 10 minutes. Water (50 ml) was added to the mixture and warmed to room temperature. The solvent was distilled off under reduced pressure, and the resulting residue was extracted with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate. The desiccant was removed by filtration. The filtrate was concentrated under reduced pressure. The resulting crude product was washed with ethanol to give 3-(1-benzenesulfonyl-1H-indol-2-yl)-3-oxo-propionitrile (47.3 g, 70%).

Workup

  1. stirringstirred for 10 minutes
  2. temperaturewarmed to room temperature
  3. distillationThe solvent was distilled off under reduced pressure
  4. extractionthe resulting residue was extracted with ethyl acetate
  5. washThe extract was washed with a saturated aqueous solution of sodium chloride
  6. dry with materialdried over anhydrous sodium sulfate
  7. customThe desiccant was removed by filtration
  8. concentrationThe filtrate was concentrated under reduced pressure
  9. washThe resulting crude product was washed with ethanol

Sources & evidence

ORD record
ord-956cc0ac5b8d4faa9ae4efdc78ef5c8d
Source dataset
uspto-grants-2014_09
Patent number
US08829199B2

Reaction notes

Loading…