P-Toluenesulfonamide → 5-Chloro-2-tosylisoindoline

HRID 425159Notes

Reaction equation

HRID 425159 reaction equation
[H-].[Na+].[C:3]1([CH3:13])[CH:8]=[CH:7][C:6]([S:9]([NH2:12])(=[O:11])=[O:10])=[CH:5][CH:4]=1.Br[CH2:15][C:16]1[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][C:17]=1[CH2:23]Br>CN(C=O)C>[Cl:22][C:19]1[CH:18]=[C:17]2[C:16](=[CH:21][CH:20]=1)[CH2:15][N:12]([S:9]([C:6]1[CH:5]=[CH:4][C:3]([CH3:13])=[CH:8][CH:7]=1)(=[O:10])=[O:11])[CH2:23]2

Participants

5

Reactant 3

HCID 6269P-ToluenesulfonamideHCID 24758Sodium hydrideHCID 150082261,2-Bis(bromomethyl)-4-chlorobenzene

Product 1

HCID 151678915-Chloro-2-tosylisoindolineYield 64.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

To a suspension of 60% sodium hydride (3 gr, 0.125 mmol) in mineral oil in 80 ml of anhydrous DMF (100 ml) was dropwise added a solution of para-toluen sulphonamide (5.6 gr, 32.60 mmol) in 30 ml of DMF over 1 hour under vigorous stirring at room temperature. After the addition, the mixture was stirred for 1 hour at room temperature and another 1 hour heating at 90° C. To this mixture was added dropwise a solution of 1,2-Bis-bromomethyl-4-chloro-benzene (4 g, 14.18 mmol) in 20 ml of anhydrous DMF at 60° C. and overnight at room temperature. The resultant mixture was poured over ice and the resulting precipitates were collected by filtration. The precipitates were washed with 1N hydrochloric acid, 5% sodium carbonate and brine. Concentration gave 2.8 gr of 5-Chloro-2-(toluene-4-sulfonyl)-2,3-dihydro-1H-isoindole as a pale yellow solid. MS: [M+H]+ 308

Workup

  1. additionAfter the addition
  2. stirringthe mixture was stirred for 1 hour at room temperature and another 1 hour
  3. temperatureheating at 90° C
  4. customovernight
  5. customat room temperature
  6. customthe resulting precipitates
  7. filtrationwere collected by filtration
  8. washThe precipitates were washed with 1N hydrochloric acid, 5% sodium carbonate and brine
  9. concentrationConcentration

Sources & evidence

ORD record
ord-a174692382ba428a90fbdc80aa745f2f
Source dataset
uspto-grants-2012_01
Patent number
US08106057B2

Reaction notes

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