Water → 5-chloro-N-(2,4-dimethoxybenzyl)-2,4-difluoro-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamide

HRID 337851Notes

Reaction equation

HRID 337851 reaction equation
[CH3:1][O:2][C:3]1[CH:15]=[C:14]([O:16][CH3:17])[CH:13]=[CH:12][C:4]=1[CH2:5][NH:6][C:7]1[S:8][CH:9]=[N:10][N:11]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[Cl:28][C:29]1[C:30]([F:40])=[CH:31][C:32]([F:39])=[C:33]([S:35](Cl)(=[O:37])=[O:36])[CH:34]=1.O>C1COCC1>[Cl:28][C:29]1[C:30]([F:40])=[CH:31][C:32]([F:39])=[C:33]([S:35]([N:6]([CH2:5][C:4]2[CH:12]=[CH:13][C:14]([O:16][CH3:17])=[CH:15][C:3]=2[O:2][CH3:1])[C:7]2[S:8][CH:9]=[N:10][N:11]=2)(=[O:37])=[O:36])[CH:34]=1

Participants

6

Reactant 4

HCID 962WaterHCID 2733832Lithium HexamethyldisilazideHCID 27735275-Chloro-2,4-difluorobenzenesulphonyl chlorideHCID 58042278N-(2,4-dimethoxybenzyl)-1,3,4-thiadiazol-2-amine

Product 1

HCID 580422535-chloro-N-(2,4-dimethoxybenzyl)-2,4-difluoro-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamideYield 58%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of N-(2,4-dimethoxybenzyl)-1,3,4-thiadiazol-2-amine (WO 2010/079443; 5.00 g, 19.9 mmol) in THF (60 mL), lithium bis(trimethylsilyl)amide (1.0 M solution in THF; 24.0 mL, 24.0 mmol) was added at −78° C. The reaction solution was stirred at room temperature for 10 minutes, and a solution of 5-chloro-2,4-difluorobenzenesulfonyl chloride (5.41 g, 21.9 mmol) in THF (15 mL) was then added thereto at −78° C. The reaction solution was stirred at room temperature for 2 hours, and water (100 mL) was then added to the reaction solution, followed by extraction with ethyl acetate (100 mL). The thus obtained organic layer was washed with saturated saline (100 mL) and dried over anhydrous sodium sulfate. After vacuum concentration, the residue was purified with silica gel chromatography (hexane/ethyl acetate=9:1) to yield the title compound (5.31 g, 58%) as a colorless solid.

Workup

  1. customat −78° C
  2. stirringThe reaction solution was stirred at room temperature for 2 hours
  3. extractionfollowed by extraction with ethyl acetate (100 mL)
  4. washThe thus obtained organic layer was washed with saturated saline (100 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationAfter vacuum concentration
  7. customthe residue was purified with silica gel chromatography (hexane/ethyl acetate=9:1)

Sources & evidence

ORD record
ord-23077ea8b6c54aad8c38b2d79f2ab2a9
Source dataset
uspto-grants-2014_11
Patent number
US08889741B2

Reaction notes

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