Cesium carbonate → 4-isopropyl-6-hydroxy-2-[1-(4-chlorophenyl)-3-trifluoromethylpyrazol-5-yl-oxymethyl]-1,2-benzisothiazol-3(2H)-one 1,1-dioxide

HRID 1289874Notes

Reaction equation

HRID 1289874 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([OH:13])=[CH:11][C:10]([C:14]([F:17])([F:16])[F:15])=[N:9]2)=[CH:4][CH:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:25][N:26]1[C:30](=[O:31])[C:29]2[C:32]([CH:37]([CH3:39])[CH3:38])=[CH:33][C:34]([OH:36])=[CH:35][C:28]=2[S:27]1(=[O:41])=[O:40]>CO>[CH:37]([C:32]1[C:29]2[C:30](=[O:31])[N:26]([CH2:25][O:13][C:12]3[N:8]([C:5]4[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=4)[N:9]=[C:10]([C:14]([F:15])([F:17])[F:16])[CH:11]=3)[S:27](=[O:41])(=[O:40])[C:28]=2[CH:35]=[C:34]([OH:36])[CH:33]=1)([CH3:39])[CH3:38]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 189225922-bromomethyl-4-isopropyl-6-hydroxy-1,2-benzisothiazol-3(2H)-one 1,1-dioxideHCID 178516154HCID 178516154, compound

Product 1

HCID 189225854-isopropyl-6-hydroxy-2-[1-(4-chlorophenyl)-3-trifluoromethylpyrazol-5-yl-oxymethyl]-1,2-benzisothiazol-3(2H)-one 1,1-dioxideYield 55%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 1-(4-chlorophenyl)-3-trifluoromethyl-5-hydroxypyrazole (8.4 g; 32 mmol) and Cs2CO3 (5.22 g; 16 mmol) in methanol (140 ml) was stirred at room temperature for 1.5 hours. The solvent was concentrated in vacuo, and the residue was dried in vacuo overnight. To the above residue was added 133 ml of DMF, cooled to 0° C., and 2-bromomethyl-4-isopropyl-6-hydroxy-1,2-benzisothiazol-3(2H)-one 1,1-dioxide (5.33 g, 16 mmol) and the resulting mixture was stirred at room temperature for 24 hours and poured into ice/water. The resulting solid was filtered, the solid was dissolved in ether (700 ml), the organic layer was washed with brine (2×200 ml), and concentrated in vacuo. The residue was purified by column chromatography (silica gel; 14-75% ethyl acetate/hexane) and recrystallized from methanol to afford 4.54 g (55%) of 4-isopropyl-6-hydroxy-2-[1-(4-chlorophenyl)-3-trifluoromethylpyrazol-5-yl-oxymethyl]-1,2-benzisothiazol-3(2H)-one 1,1-dioxide (Formula I: R1 =4-Cl--Ph; R2 =CH3 ; R3 =H; R4 =CH(CH3)2 ; R5 =6-OH) as a white solid.

Workup

  1. concentrationThe solvent was concentrated in vacuo
  2. customthe residue was dried in vacuo overnight
  3. additionTo the above residue was added 133 ml of DMF
  4. temperaturecooled to 0° C.
  5. filtrationThe resulting solid was filtered
  6. dissolutionthe solid was dissolved in ether (700 ml)
  7. washthe organic layer was washed with brine (2×200 ml)
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by column chromatography (silica gel; 14-75% ethyl acetate/hexane)
  10. customrecrystallized from methanol

Sources & evidence

ORD record
ord-5809f147837c41619cdd75ac0948bfb4
Source dataset
uspto-grants-1998_05
Patent number
US05750550

Reaction notes

Loading…