Methanol → HCID 178498985, compound

HRID 335517Notes

Reaction equation

HRID 335517 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:6]([O:14]C(OC)=O)=[N:7][S:8][C:9]=1[S:10]([CH3:13])(=[O:12])=[O:11])=[O:4].ClCCl.CO.S(=O)(=O)(O)O>O>[CH3:1][O:2][C:3]([C:5]1[C:6]([OH:14])=[N:7][S:8][C:9]=1[S:10]([CH3:13])(=[O:12])=[O:11])=[O:4]

Participants

5

Reactant 3

HCID 887MethanolHCID 1118Sulfuric AcidHCID 86626435HCID 86626435, compound

Product 1

HCID 178498985HCID 178498985, compoundYield 80%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
65 °C

Procedure

The 5-Methanesulfonyl-3-methoxycarbonyloxy-isothiazole-4-carboxylic acid methyl ester/dichloromethane extracts were combined, then displaced with methanol (150 mL, 15 volumes). A solution of 98% sulfuric acid (50 mL, 5 volumes) in water (100 mL, 10 volumes) was added and the mixture was heated at 65° C. for 6 hours. The foamy slurry became a clear solution with some insoluble white solids over time. The mixture was cooled to 25° C. and stirred for 16 hours. Most of the methanol was removed under vacuum. The aqueous residue was extracted once with 100 mL dichloromethane, then twice with 50 mL dichloromethane. The combined dichloromethane extracts were dried over anhydrous magnesium sulfate and filtered. The dichloromethane was displaced with hexanes (100 mL, 10 volumes) and stirred at 25° C. until solids formed. The solids were filtered, and the filter cake was rinsed with hexane and dried to give 9.27 g of 3-Hydroxy-5-methanesulfonyl-isothiazole-4-carboxylic acid methyl ester (80% yield). 1H NMR (DMSO-d6): δ 13.07 (s, 1H); 3.83 (s, 3H); 3.55 (s, 3H). MS (API-ES pos): 238 (M+H)+; 206 (M-MeO)+, base.

Workup

  1. temperatureThe mixture was cooled to 25° C.
  2. customMost of the methanol was removed under vacuum
  3. extractionThe aqueous residue was extracted once with 100 mL dichloromethane
  4. dry with materialThe combined dichloromethane extracts were dried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. stirringstirred at 25° C. until solids
  7. customformed
  8. filtrationThe solids were filtered
  9. washthe filter cake was rinsed with hexane
  10. customdried

Sources & evidence

ORD record
ord-bc978b8af12e4cd48ed73887bcae4a6e
Source dataset
uspto-grants-2014_11
Patent number
US08884025B2

Reaction notes

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