Chlorosulfonic acid → 1,2-Benzisoxazole-3-methanesulfonic acid

HRID 2223686Notes

Reaction equation

HRID 2223686 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[C:3]([CH2:10]C(O)=O)=[N:2]1.Cl[S:15]([OH:18])(=[O:17])=[O:16]>O1CCOCC1>[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[C:3]([CH2:10][S:15]([OH:18])(=[O:17])=[O:16])=[N:2]1

Participants

4

Reactant 2

HCID 24638Chlorosulfonic acidHCID 3017292-(1,2-Benzoxazol-3-yl)acetic acid

Product 1

HCID 98777711,2-Benzisoxazole-3-methanesulfonic acidYield 90.6%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
62.5 °C

Procedure

1,2-Benzisoxazole-3-acetic acid (200 g; 1.13 mol) was suspended in 1,4-dioxane (600 mL). The mixture was cooled in an ice-bath and chlorosulfonic acid (82.6 mL, 1.24 mol, 1.1 eq) was added maintaining the internal temperature below 20° C. The mixture was heated to 60-65° C. for 9½ h and cooled to room-temperature. CELITE™ (20 g) was added followed by xylenes (1000 mL) and the mixture was stirred for one hour at room temperature. It was filtered and concentrated. The suspension obtained was heated to 50-60° C. for three hours and then gradually cooled to 0-5° C. and filtered. The precipitate was filtered off under a nitrogen atmosphere and washed with 400 mL 1,4-dioxane/xylenes (v/v=1:9). It was dried at 60° C. for approximately 16 hours in a vacuum oven (≦1 mm Hg) to give 218.14 g crystalline anhydrous 1,2-benzisoxazole-3-methanesulfonic acid (90.6%) with a HPLC purity of 99.4%.

Workup

  1. temperatureThe mixture was cooled in an ice-bath
  2. temperaturemaintaining the internal temperature below 20° C
  3. temperaturecooled to room-temperature
  4. additionwas added
  5. filtrationIt was filtered
  6. concentrationconcentrated
  7. customThe suspension obtained
  8. temperaturewas heated to 50-60° C. for three hours
  9. temperaturegradually cooled to 0-5° C.
  10. filtrationfiltered
  11. filtrationThe precipitate was filtered off under a nitrogen atmosphere
  12. washwashed with 400 mL 1,4-dioxane/xylenes (v/v=1:9)
  13. customIt was dried at 60° C. for approximately 16 hours in a vacuum oven (≦1 mm Hg)

Sources & evidence

ORD record
ord-1096107d3f934f9bb8d0bda879e54f8f
Source dataset
uspto-grants-2008_05
Patent number
US07375233B2

Reaction notes

Loading…