Tetrahydrofuran → 3-(N-(4-Chloro-3-methylisoxazol-5-yl)sulfamoyl)thiophene-2-carboxylic acid

HRID 2047257Notes

Reaction equation

HRID 2047257 reaction equation
[H-].[Na+].O1CCCC1.[Cl:8][C:9]1[C:10]([CH3:15])=[N:11][O:12][C:13]=1[NH2:14].Cl[S:17]([C:20]1[CH:24]=[CH:23][S:22][C:21]=1[C:25]([O:27]C)=[O:26])(=[O:19])=[O:18]>CCCCCC>[Cl:8][C:9]1[C:10]([CH3:15])=[N:11][O:12][C:13]=1[NH:14][S:17]([C:20]1[CH:24]=[CH:23][S:22][C:21]=1[C:25]([OH:27])=[O:26])(=[O:18])=[O:19]

Participants

6

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 24758Sodium hydrideHCID 27367332-Thiophenecarboxylic acid, 3-(chlorosulfonyl)-, methyl esterHCID 105828224-Chloro-3-methyl-1,2-oxazol-5-amine

Product 1

HCID 108058203-(N-(4-Chloro-3-methylisoxazol-5-yl)sulfamoyl)thiophene-2-carboxylic acidYield 35.2%

Reagents, catalysts & solvents 1

HCID 8058HexaneSolvent

Procedure

To a mixture of sodium hydride (60%, 2.1 g, 52 mmol) and tetrahydrofuran (20 mL) was added a mixture of 4-chloro-3-methyl-1,2-oxazol-5-amine (3.0 g, 23 mmol) and tetrahydrofuran (20 mL) at 0° C., followed by stirring at that temperature for 30 minutes. Methyl 3-(chlorosulfonyl)thiophene-2-carboxylate (5.3 g, 22 mmol) was added at that temperature to the reaction mixture, which was then stirred for 1 hour at 0° C., and then stirred for 4 hours at room temperature. Hexane (100 ml) was added at room temperature to the reaction mixture, and the precipitated solid was collected by filtration. Methanol (20 mL) was added to the solid, followed by a 2N aqueous solution of sodium hydroxide (20 mL), and the reaction mixture was stirred for 5 hours at room temperature. The solvent was distilled away under reduced pressure, and ice water (20 mL) was added to the residue, followed by a 2 N aqueous solution of hydrochloric acid (20 mL). The precipitated solid was collected by filtration to give the title compound (2.5 g, 35% yield).

Workup

  1. additionwas added
  2. stirringwas then stirred for 1 hour at 0° C.
  3. stirringstirred for 4 hours at room temperature
  4. filtrationthe precipitated solid was collected by filtration
  5. additionMethanol (20 mL) was added to the solid
  6. stirringthe reaction mixture was stirred for 5 hours at room temperature
  7. distillationThe solvent was distilled away under reduced pressure, and ice water (20 mL)
  8. additionwas added to the residue
  9. filtrationThe precipitated solid was collected by filtration

Sources & evidence

ORD record
ord-134d480e44b7455992fa6d72039dd9fa
Source dataset
uspto-grants-2013_11
Patent number
US08592470B2

Reaction notes

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