Sodium hydride → N-(4-bromo-3-methyl-5-isoxazolyl)-5-(3-isoxazolyl)thiophene-2-sulfonamide

HRID 1899604Notes

Reaction equation

HRID 1899604 reaction equation
[NH2:1][C:2]1[O:6][N:5]=[C:4]([CH3:7])[C:3]=1[Br:8].[H-].[Na+].[O:11]1[CH:15]=[CH:14][C:13]([C:16]2[S:20][C:19]([S:21](Cl)(=[O:23])=[O:22])=[CH:18][CH:17]=2)=[N:12]1>C1COCC1>[Br:8][C:3]1[C:4]([CH3:7])=[N:5][O:6][C:2]=1[NH:1][S:21]([C:19]1[S:20][C:16]([C:13]2[CH:14]=[CH:15][O:11][N:12]=2)=[CH:17][CH:18]=1)(=[O:22])=[O:23]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27971805-(Isoxazol-3-yl)thiophene-2-sulfonyl chlorideHCID 104875194-Bromo-3-methylisoxazol-5-amine

Product 1

HCID 15342057N-(4-bromo-3-methyl-5-isoxazolyl)-5-(3-isoxazolyl)thiophene-2-sulfonamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of 5-amino-4-bromo-3-methylisoxazole (177 mg, 1.0 mmol) in dry THF (2 ml) was added to a suspension of sodium hydride (60% dispersion in mineral oil, 90 mg, 2.2 mmol) in dry THF (1 ml) at 0°-5° C. After stirring at 0°-5° C. for 5 min, the reaction was warmed to room temperature for 10 min to complete the reaction. The reaction mixture was re-cooled to 0° C., and 5-(3-isoxazolyl)thiophene-2-sulphonyl chloride (273 mg, 1.1 mmol), which had been dissolved in dry THF (2 ml), was added slowly. Stirring was continued for 1 h; during this period the reaction mixture slowly attained ambient temperature. THF was removed under reduced pressure. The residue was dissolved in water (10 ml), the pH was adjusted to 2-3 by adding concentrated HCl, and was extracted with methylene chloride (3×10 ml). The combined organic layers was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give N-(4-bromo-3-methyl-5-isoxazolyl)-5-(3-isoxazolyl)thiophene-2-sulfonamide. The pure material was obtained by recrystallization using hexanes/ethyl acetate (160 mg, 41% yield), m.p. 120°-123° C.

Workup

  1. customthe reaction
  2. temperatureThe reaction mixture was re-cooled to 0° C.
  3. additionwas added slowly
  4. stirringStirring
  5. waitwas continued for 1 h
  6. waitduring this period the reaction mixture slowly attained ambient temperature
  7. customTHF was removed under reduced pressure
  8. dissolutionThe residue was dissolved in water (10 ml)
  9. additionby adding concentrated HCl
  10. extractionwas extracted with methylene chloride (3×10 ml)
  11. dry with materialThe combined organic layers was dried over anhydrous magnesium sulfate
  12. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-8681a92027014237aece26eb1e185604
Source dataset
uspto-grants-1996_11
Patent number
US05571821

Reaction notes

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