Potassium Iodide → HCID 19786588, compound

HRID 1646740Notes

Reaction equation

HRID 1646740 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.[N:37]1[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=1[N:43]1[CH2:48][CH2:47][NH:46][CH2:45][CH2:44]1.[I-].[K+]>CN(C=O)C>[F:19][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=1[C:10]1[C:9]2[C:20](=[O:21])[CH:5]([CH2:4][CH2:3][CH2:2][N:46]3[CH2:47][CH2:48][N:43]([C:38]4[CH:39]=[CH:40][CH:41]=[CH:42][N:37]=4)[CH2:44][CH2:45]3)[CH2:6][CH2:7][C:8]=2[O:12][N:11]=1

Participants

7

Reactant 5

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 81531DiisopropylethylamineHCID 944591-(2-Pyridyl)piperazineHCID 19786560HCID 19786560, compound

Product 1

HCID 19786588HCID 19786588, compound

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 (6.4 g) and DMF (100 ml) was added anhydrous potassium carbonate (1.4 g), diisopropylethyl amine (5.4 ml), 1-(2-pyridyl)piperazine (4.8 ml) and potassium iodide (0.4 g) at room temperature with stirring. The flask was flushed with nitrogen and warmed to 80° C. for 16 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 three times with ethyl acetate. The combined organic layers were washed with water twice, then brine and dried (MgSO4). Filtration and concentration gave the crude product. Purification via preparative HPLC (silica gel, 3% methanol) afforded 4.2 g of 6,7-dihydro-3-(2-fluorophenyl)-5-[3-(4-(2-pyridyl)-1-piperazinyl)-propyl]-1,2-benzisoxazol-4(5H)-one, as an oil which solidified upon standing. The product was recrystallized from ether, m.p. 94°-96° 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 three times with ethyl acetate
  6. washThe combined organic layers were washed with water twice
  7. dry with materialbrine and dried (MgSO4)
  8. filtrationFiltration and concentration
  9. customgave the crude product
  10. customPurification via preparative HPLC (silica gel, 3% methanol)

Sources & evidence

ORD record
ord-b33e9b313c1546c28021f01ad8d6a148
Source dataset
uspto-grants-1993_01
Patent number
US05180834

Reaction notes

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