Sodium Hydroxide → 4-[(1,2,4-Thiadiazol-5-ylamino)sulfonyl]benzoic acid

HRID 1808193Notes

Reaction equation

HRID 1808193 reaction equation
[NH2:1][C:2]1[S:6][N:5]=[CH:4][N:3]=1.[Li].FC1C([O:15][S:16]([C:19]2[CH:28]=[CH:27][C:22]([C:23]([O:25]C)=[O:24])=[CH:21][CH:20]=2)(=O)=[O:17])=C(F)C(F)=C(F)C=1F.[OH-].[Na+]>C1COCC1.O>[S:6]1[C:2]([NH:1][S:16]([C:19]2[CH:20]=[CH:21][C:22]([C:23]([OH:25])=[O:24])=[CH:27][CH:28]=2)(=[O:17])=[O:15])=[N:3][CH:4]=[N:5]1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 2902745-Amino-1,2,4-thiadiazoleHCID 3028194LithiumHCID 57732203Methyl 4-[(pentafluorophenoxy)sulfonyl]benzoate

Product 1

HCID 577322144-[(1,2,4-Thiadiazol-5-ylamino)sulfonyl]benzoic acidYield 43%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-amino-1,2,4-thiadiazole (58 mg, 0.574 mmol, 1.1 eq) in THF (5 ml) was added, 1,1,3,3,3-Hexanemethyldisilazane lithium salt (LiHMDS, 1M in THF, 1.15 ml, 1.2 mmol, 2.2 eq) and the reaction mixture stirred at 50° C. for 5 minutes. Methyl 4-[(pentafluorophenoxy)sulfonyl]benzoate (Preparation 28, 196 mg, 0.513 mmol, 1 eq) was added and the reaction monitored. On the disappearance of the starting materials the reaction mixture was quenched with water (5 ml), diluted with ethyl acetate (10 ml), washed with saturated sodium hydrogen carbonate, dried over sodium sulphate, filtered and evaporated in vacuo. The residue was dissolved in dioxane (5 ml) and a solution of sodium hydroxide (100 mg, 2.5 mmol, 4.3 eq) in water (2 ml) was added and the reaction mixture stirred at room temperature for 30 minutes. The reaction mixture was partitioned between ethyl acetate (5 ml) and water (5 ml), the aqueous phase was acidified with concentrated HCl, extracted into ethyl acetate (10 ml), dried over sodium sulphate, filtered and evaporated in vacuo. The crude material was triturated with DCM to yield the title compound as a pale yellow solid (64 mg, 0.22 mmol, 43%).

Workup

  1. customOn the disappearance of the starting materials the reaction mixture was quenched with water (5 ml)
  2. additiondiluted with ethyl acetate (10 ml)
  3. washwashed with saturated sodium hydrogen carbonate
  4. dry with materialdried over sodium sulphate
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. dissolutionThe residue was dissolved in dioxane (5 ml)
  8. customThe reaction mixture was partitioned between ethyl acetate (5 ml) and water (5 ml)
  9. extractionextracted into ethyl acetate (10 ml)
  10. dry with materialdried over sodium sulphate
  11. filtrationfiltered
  12. customevaporated in vacuo
  13. customThe crude material was triturated with DCM

Sources & evidence

ORD record
ord-6798cc8ec440453b8848858464fee7a9
Source dataset
uspto-grants-2013_01
Patent number
US08357711B2

Reaction notes

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