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

HRID 1289868Notes

Reaction equation

HRID 1289868 reaction equation
[C:1]1([N:7]2[C:11]([OH:12])=[CH:10][C:9]([C:13]([F:16])([F:15])[F:14])=[N:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:24][N:25]1[C:29](=[O:30])[C:28]2[C:31]([CH:36]([CH3:38])[CH3:37])=[CH:32][C:33]([OH:35])=[CH:34][C:27]=2[S:26]1(=[O:40])=[O:39].CCOCC.[Cl-].[Na+].O>CO.CN(C=O)C>[CH:36]([C:31]1[C:28]2[C:29](=[O:30])[N:25]([CH2:24][O:12][C:11]3[N:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)[N:8]=[C:9]([C:13]([F:15])([F:16])[F:14])[CH:10]=3)[S:26](=[O:40])(=[O:39])[C:27]=2[CH:34]=[C:33]([OH:35])[CH:32]=1)([CH3:38])[CH3:37]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 189225922-bromomethyl-4-isopropyl-6-hydroxy-1,2-benzisothiazol-3(2H)-one 1,1-dioxideHCID 131720641Ether brineHCID 178516151HCID 178516151, compound

Product 1

HCID 189225714-isopropyl-6-hydroxy-2-(1-phenyl-3-trifluoromethylpyrazol-5-yl-oxymethyl)-1,2-benzisothiazol-3(2H)-one 1,1-dioxideYield 71.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
20 °C

Procedure

A mixture 1-phenyl-3-trifluoromethyl-5-hydroxypyrazole (20.5 g; 89.92 mmol) and Cs2CO3 (17.6 g; 53.8 mmol) in methanol (50 ml) was stirred at 20° C. for 5 hours. The solvent was concentrated in vacuo, and the residue was dried in vacuo at 50° C. for 4 hours. To a solution of the above residue in 50 ml of DMF was added 2-bromomethyl-4-isopropyl-6-hydroxy-1,2-benzisothiazol-3(2H)-one 1,1-dioxide (25 g, 74.9 mmol) and the resulting mixture was stirred at room temperature (20° C.) overnight and poured into ether/brine. The above mixture was extracted with ether and the combined organic layer was dried over sodium sulfate, and concentrated in vacuo. The residue (46 g) was purified by column chromatography (silica gel; chloroform, 2% ethyl acetate in chloroform) and recrystallized from hexane to afford 25.7 g (71%) of 4-isopropyl-6-hydroxy-2-(1-phenyl-3-trifluoromethylpyrazol-5-yl-oxymethyl)-1,2-benzisothiazol-3(2H)-one 1,1-dioxide (Formula I: R1 =Ph; R2 =CF3 ; 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 at 50° C. for 4 hours
  3. extractionThe above mixture was extracted with ether
  4. dry with materialthe combined organic layer was dried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue (46 g) was purified by column chromatography (silica gel; chloroform, 2% ethyl acetate in chloroform)
  7. customrecrystallized from hexane

Sources & evidence

ORD record
ord-875b7e0ff78647e78153e75045a10d40
Source dataset
uspto-grants-1998_05
Patent number
US05750550

Reaction notes

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