Toluene → 1,2-Benzoxazol-3-ylmethanesulfonimidic acid

HRID 19745Notes

Reaction equation

HRID 19745 reaction equation
C[O:2][S:3]([CH2:6][C:7]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[O:9][N:8]=1)(=O)=[O:4].C1(C)C=CC=CC=1.C[N:24](C=O)C.C(Cl)(=O)C(Cl)=O>O>[CH:13]1[CH:14]=[CH:15][C:10]2[O:9][N:8]=[C:7]([CH2:6][S:3]([OH:2])(=[O:4])=[NH:24])[C:11]=2[CH:12]=1

Participants

6

Reactant 4

HCID 1140TolueneHCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 86602676HCID 86602676, compound

Product 1

HCID 119678001,2-Benzoxazol-3-ylmethanesulfonimidic acidYield 80.4%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
10 °C

Procedure

A 250 ml three necked flask, equipped with mechanical stirrer, Dean-Stark trap and condenser, was charged with 1,2-benzisoxazole-3-methanesulfonic acid methyl ester (10 grams, 0.044 mole, obtained from a commercial vendor) and toluene (100 ml). The suspension was heated to reflux while azeotropic distillation of water was performed, during 2 hours. The mixture was thereafter cooled under nitrogen atmosphere to 10° C. and DMF (0.36 ml, 0.0044 mole, 0.1 molar equivalent) was added to the mixture. Oxalyl chloride (4.1 ml, 0.047 mole, 1.07 molar equivalent) was then added drop-wise at 10-15° C. during 30 minutes and the reaction mixture was heated to 40° C. and was kept at this temperature for 4 hours. Ammonia (gas) (3.0 grams, 4 molar equivalents) was then bubbled into the reaction mixture at 10-18° C. during 2 hours and the reaction mixture was kept at ambient temperature overnight. The obtained precipitate was collected by filtration and slurried in 25% ammonium hydroxide (40 ml) at ambient temperature for 2 hours. The obtained solid was collected by filtration, washed with water and dried under reduced pressure at 50° C., overnight to obtain crude zonisamide (7.4 grams, 80.4% yield) having a purity of 98.7%, as determined by HPLC.

Workup

  1. temperatureThe suspension was heated
  2. temperaturethe reaction mixture was heated to 40° C.
  3. waitwas kept at this temperature for 4 hours
  4. customAmmonia (gas) (3.0 grams, 4 molar equivalents) was then bubbled into the reaction mixture at 10-18° C. during 2 hours
  5. waitthe reaction mixture was kept at ambient temperature overnight
  6. filtrationThe obtained precipitate was collected by filtration
  7. waitslurried in 25% ammonium hydroxide (40 ml) at ambient temperature for 2 hours
  8. filtrationThe obtained solid was collected by filtration
  9. washwashed with water
  10. customdried under reduced pressure at 50° C., overnight

Sources & evidence

ORD record
ord-5261ef186927439bb977d5deee8ad015
Source dataset
uspto-grants-2010_06
Patent number
US07745471B2

Reaction notes

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