Benzenesulfonyl chloride → 3-(2-Ethoxypyridin-3-yl)-3-hydroxy-2-oxo-1-(phenylsulfonyl)indoline-5-carbonitrile

HRID 1484615Notes

Reaction equation

HRID 1484615 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[C:6]2([OH:22])[C:13]1[C:14]([O:19][CH2:20][CH3:21])=[N:15][CH:16]=[CH:17][CH:18]=1)#[N:2].CC(C)([O-])C.[K+].[C:29]1([S:35](Cl)(=[O:37])=[O:36])[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.ClCCl.CO>CN(C)C=O>[CH2:20]([O:19][C:14]1[C:13]([C:6]2([OH:22])[C:5]3[C:9](=[CH:10][CH:11]=[C:3]([C:1]#[N:2])[CH:4]=3)[N:8]([S:35]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)(=[O:37])=[O:36])[C:7]2=[O:12])=[CH:18][CH:17]=[CH:16][N:15]=1)[CH3:21]

Participants

6

Reactant 4

HCID 7369Benzenesulfonyl chlorideHCID 21226129Dichloromethane methanolHCID 23665647Potassium tert-butoxideHCID 670486385-Cyano-3-hydroxy-3-(2-ethoxypyridin-3-yl)-1,3-dihydroindol-2-one

Product 1

HCID 685568513-(2-Ethoxypyridin-3-yl)-3-hydroxy-2-oxo-1-(phenylsulfonyl)indoline-5-carbonitrileYield 78.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

2.50 g (7.79 mmol) of (−)-5-cyano-3-hydroxy-3-(2-ethoxypyridin-3-yl)-1,3-dihydroindol-2-one (prepared as in example 1.2 and racemate resolution into the corresponding enantiomers as described above) were dissolved in 30 ml of dimethylformamide, resulting in a yellow solution. After cooling to 0° C., 1.00 g (8.94 mmol) of potassium tert-butoxide was added in portions so that the temperature was kept between 0° C. and 5° C. The solution changed in color from yellow to dark yellow. It was stirred for 30 minutes and, at 0° C., 1.07 ml (8.20 mmol) of benzenesulfonyl chloride were slowly added dropwise. The solution became turbid and pale orange in color. It was stirred while cooling in ice for one hour. The progress of the reaction was followed by thin-layer chromatography (dichloromethane/methanol 9:1). For working up, the reaction mixture was added dropwise to ice-water. During this, a precipitate separated out and was, after stirring for 5 minutes, filtered off and washed with water. The title compound (2.65 g, 6.09 mmol, 78%) was dried in a vacuum drying oven at 40° C. and used for the next reaction without further purification.

Workup

  1. customresulting in a yellow solution
  2. customwas kept between 0° C. and 5° C
  3. stirringIt was stirred
  4. temperaturewhile cooling in ice for one hour
  5. customDuring this, a precipitate separated out and
  6. stirringafter stirring for 5 minutes
  7. filtrationfiltered off
  8. washwashed with water

Sources & evidence

ORD record
ord-1aa7ddbc36264eb98fbd72da088e2370
Source dataset
uspto-grants-2016_08
Patent number
US09422264B2

Reaction notes

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