Sodium hydride → Methyl 4-(5-fluoro-3-methylbenzo[b]thiophene-2-sulfonylamino)-3-methanesulfonylbenzoate

HRID 748488Notes

Reaction equation

HRID 748488 reaction equation
[NH2:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[S:12]([CH3:15])(=[O:14])=[O:13].[H-].[Na+].Cl[S:19]([C:22]1[S:26][C:25]2[CH:27]=[CH:28][C:29]([F:31])=[CH:30][C:24]=2[C:23]=1[CH3:32])(=[O:21])=[O:20]>C1COCC1>[F:31][C:29]1[CH:28]=[CH:27][C:25]2[S:26][C:22]([S:19]([NH:1][C:2]3[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=3[S:12]([CH3:15])(=[O:14])=[O:13])(=[O:20])=[O:21])=[C:23]([CH3:32])[C:24]=2[CH:30]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27745865-Fluoro-3-methylbenzo[b]thiophene-2-sulphonyl chlorideHCID 22041468methyl 4-Amino-3-methylsulfonylbenzoate

Product 1

HCID 9825353Methyl 4-(5-fluoro-3-methylbenzo[b]thiophene-2-sulfonylamino)-3-methanesulfonylbenzoateYield 89.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Into 300 mL of THF was dissolved 14.0 g of methyl 4-amino-3-methanesulfonylbenzoate, followed by addition of 6.10 g of sodium hydride (oily, 60%) at 0° C. After 40 minutes of stirring at the same temperature, 16.0 g of 2-chlorosulfonyl-5-fluoro-3-methylbenzo[b]thiophene was added at 0° C. followed by 3 hours of stirring at room temperature. After confirmation of disappearance of the starting material, the reaction was terminated by adding 2 mol/L hydrochloric acid at 0° C., followed by extraction with ethyl acetate. The organic layer was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine and then dried over anhydrous sodium sulfate. The solvent was removed by evaporation and the residue was diluted with ethyl acetate. After the solution was treated with active carbon, purification by recrystallization (ethyl acetate/ether) afforded 24.8 g of the title compound as colorless powder.

Workup

  1. additionwas added at 0° C.
  2. customAfter confirmation of disappearance of the starting material, the reaction was terminated
  3. additionby adding 2 mol/L hydrochloric acid at 0° C.
  4. extractionfollowed by extraction with ethyl acetate
  5. washThe organic layer was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. customThe solvent was removed by evaporation
  8. additionthe residue was diluted with ethyl acetate
  9. additionAfter the solution was treated with active carbon, purification by recrystallization (ethyl acetate/ether)

Sources & evidence

ORD record
ord-3e277163380c440180df0ee4da0b9e8e
Source dataset
uspto-grants-2008_07
Patent number
US07399781B2

Reaction notes

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