Potassium Iodide → HCID 19786550, compound

HRID 1657109Notes

Reaction equation

HRID 1657109 reaction equation
Cl[CH2:2][CH2:3][CH2:4][CH:5]1[C:20](=[O:21])[C:9]2[C:10]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[F:19])=[N:11][O:12][C:8]=2[CH2:7][CH2:6]1.C(=O)([O-])[O-].[K+].[K+].C(N(C(C)C)CC)(C)C.[F:37][C:38]1[CH:43]=[CH:42][C:41]([N:44]2[CH2:49][CH2:48][NH:47][CH2:46][CH2:45]2)=[CH:40][CH:39]=1.[I-].[K+]>CN(C=O)C>[F:37][C:38]1[CH:39]=[CH:40][C:41]([N:44]2[CH2:49][CH2:48][N:47]([CH2:2][CH2:3][CH2:4][CH:5]3[C:20](=[O:21])[C:9]4[C:10]([C:13]5[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=5[F:19])=[N:11][O:12][C:8]=4[CH2:7][CH2:6]3)[CH2:46][CH2:45]2)=[CH:42][CH:43]=1

Participants

7

Reactant 5

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 752601-(4-Fluorophenyl)piperazineHCID 81531DiisopropylethylamineHCID 19786560HCID 19786560, compound

Product 1

HCID 19786550HCID 19786550, compoundYield 47%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution consisting of 5-(3-chloropropyl)-3-(2-fluorophenyl)-6,7-dihydro -1,2-benzisoxazol-4(5H)-one (5.8 g) and DMF (100 ml) was added anhydrous potassium carbonate (1.3 g), diisopropylethyl amine (4.9 ml), 1-(4-fluorophenyl)piperazine (4.1 g) and potassium iodide (0.3 g) at room temperature with stirring. The flask was flushed with nitrogen and warmed to 80° C. for 13.5 hours. Upon cooling to room temperature, water and ethyl acetate were added to the reaction mixture. The layers were separated and the aqueous phase was extracted 3 times with ethyl acetate. The combined organic layers were washed with water twice, brine, and then dried (MgSO4). Filtration and concentration gave the crude product. Purification via flash column chromatography (silica gel, 2% triethylamine/ether) afforded 4.0 g of 6,7-dihydro-5-[3-(4-(4-fluorophenyl)-1-piperazinyl)-propyl]-3-(2-fluorophenyl)-1,2-benzisoxazol -4(5H)-one as an oil. The product was flushed thru alumina with ether. The hydrochloride was prepared in ether with ethereal HCl. The precipitate was filtered and washed with pentane, m.p. 161°-164° C.

Workup

  1. customThe flask was flushed with nitrogen
  2. temperatureUpon cooling to room temperature
  3. additionwater and ethyl acetate were added to the reaction mixture
  4. customThe layers were separated
  5. extractionthe aqueous phase was extracted 3 times with ethyl acetate
  6. washThe combined organic layers were washed with water twice
  7. dry with materialbrine, and then dried (MgSO4)
  8. filtrationFiltration and concentration
  9. customgave the crude product
  10. customPurification via flash column chromatography (silica gel, 2% triethylamine/ether)

Sources & evidence

ORD record
ord-a21e43aa93ff4cc19b3b47f67a145fa0
Source dataset
uspto-grants-1993_10
Patent number
US05256672

Reaction notes

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