P-Toluenesulfonamide → 4,7-Difluoro-2-(toluene-4-sulfonyl)isoindoline

HRID 334892Notes

Reaction equation

HRID 334892 reaction equation
[C:1]1([CH3:11])[CH:6]=[CH:5][C:4]([S:7]([NH2:10])(=[O:9])=[O:8])=[CH:3][CH:2]=1.[H-].[Na+].Br[CH2:15][C:16]1[C:21]([CH2:22]Br)=[C:20]([F:24])[CH:19]=[CH:18][C:17]=1[F:25]>CN(C)C=O>[F:24][C:20]1[CH:19]=[CH:18][C:17]([F:25])=[C:16]2[C:21]=1[CH2:22][N:10]([S:7]([C:4]1[CH:3]=[CH:2][C:1]([CH3:11])=[CH:6][CH:5]=1)(=[O:8])=[O:9])[CH2:15]2

Participants

5

Reactant 3

HCID 6269P-ToluenesulfonamideHCID 24758Sodium hydrideHCID 593822902,3-Bis-bromomethyl-1,4-difluorobenzene

Product 1

HCID 593822484,7-Difluoro-2-(toluene-4-sulfonyl)isoindolineYield 56%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
60 °C

Procedure

A solution of 4-toluenesulphonamide (2.44 g, 14.28 mmol) in N,N-dimethylformamide (10 ml) was added dropwise to a vigourously stirred suspension of sodium hydride (1.2 g, 60 wt % in mineral oil, 30.0 mmol) in anhydrous N,N-dimethylformamide (60 ml). The mixture was strirred at room temperature for 1 hour, at 110° C. for 1 hour and was then cooled to 60° C. and a solution of 2,3-bis-bromomethyl-1,4-difluorobenzene (4.28 g, 14.28 mmol) in N,N-dimethylformamide (30 ml) was added dropwise. The mixture was stirred at 60° C. for 1 hour and then at room temperature for 16 hours. The solvent was removed in vacuo and the residue partitioned between dichloromethane and 1M hydrochloric acid. The organic layer was separated, washed with 5% aqueous potassium carbonate solution, the organics were separated and the solvent removed in vacuo. The residue was rinsed with diethyl ether, filtered and the solids sucked dry under reduced pressure to afford 4,7-difluoro-2-(toluene-4-sulfonyl)isoindoline (2.46 g, 56%) as a pale tan solid. 1H NMR (DMSO-d6) 7.82 (2H, d), 7.43 (2H, d), 7.15 (2H, dd), 4.66 (4H, s), 2.36 (3H, s). MS: [M+H]+ 310.

Workup

  1. waitat room temperature for 16 hours
  2. customThe solvent was removed in vacuo
  3. customthe residue partitioned between dichloromethane and 1M hydrochloric acid
  4. customThe organic layer was separated
  5. washwashed with 5% aqueous potassium carbonate solution
  6. customthe organics were separated
  7. customthe solvent removed in vacuo
  8. washThe residue was rinsed with diethyl ether
  9. filtrationfiltered
  10. customthe solids sucked dry under reduced pressure

Sources & evidence

ORD record
ord-8ddddae153b54f81a75b6af372efe9f4
Source dataset
uspto-grants-2014_11
Patent number
US08883790B2

Reaction notes

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