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

HRID 250217Notes

Reaction equation

HRID 250217 reaction equation
[H-].[Na+].[NH2:3][C:4]1[O:8][N:7]=[C:6]([CH3:9])[C:5]=1[Cl:10].C[O:12][C:13]([C:15]1[S:16][CH:17]=[CH:18][C:19]=1[S:20](Cl)(=[O:22])=[O:21])=[O:14]>O1CCCC1>[Cl:10][C:5]1[C:6]([CH3:9])=[N:7][O:8][C:4]=1[NH:3][S:20]([C:19]1[CH:18]=[CH:17][S:16][C:15]=1[C:13]([OH:14])=[O:12])(=[O:21])=[O:22]

Participants

5

Reactant 3

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 45.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

At about 0° C., sodium hydride (60% dispersion in mineral oil, 458 mg, 19 mmol) was added to a solution of 5-amino-4-chloro-3-methylisoxazole (1.1 g, 8.3 mmol) in anhydrous tetrahydrofuran (30 mL). The resulting mixture was stirred for about 10 minutes and 2-(methoxycarbonyl)thiophene-3-sulfonyl chloride (1.95 g, 8.11 mmol) was slowly added. Under continuous stirring, the mixture was maintained at ambient temperature for about 4 hours. The mixture was then diluted with hexanes (30 mL) and the resulting precipitate was filtered and washed with hexanes. The precipitate was then dissolved in 1 N sodium hydroxide and stirred at ambient temperature for about 1 hour. After acidifying to pH ˜2 with 2 N hydrochloric acid, the resulting precipitate was filtered, washed with water, and dried in vacuo to give the desired product 3-[(4-chloro-3-methyl-5-isoxazolyl)sulfamoyl]-2-thiophenecarboxylic acid (1.2 g, 45%) as a yellow powder. 1H NMR (300 MHz, CD3OD) δ 7.82 (d, J=5.4 Hz, 1H), 7.53 (d, J=5.4 Hz, 1H), 2.24 (s, 3H); LC-MS: m/z=323 (MH)+.

Workup

  1. filtrationthe resulting precipitate was filtered
  2. washwashed with hexanes
  3. dissolutionThe precipitate was then dissolved in 1 N sodium hydroxide
  4. stirringstirred at ambient temperature for about 1 hour
  5. filtrationthe resulting precipitate was filtered
  6. washwashed with water
  7. customdried in vacuo

Sources & evidence

ORD record
ord-4300a32a5bbb466f8df7ee8f71f21a10
Source dataset
uspto-grants-2011_01
Patent number
US07863308B2

Reaction notes

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