Water → 2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]-1-(2,3-dihydro-1H-isoindol-2-yl)ethanone

HRID 744443Notes

Reaction equation

HRID 744443 reaction equation
[F:1][C:2]1[CH:20]=[CH:19][C:5]2[C:6]([CH:9]3[CH2:14][CH2:13][N:12]([CH2:15][C:16]([NH2:18])=[O:17])[CH2:11][CH2:10]3)=[N:7][O:8][C:4]=2[CH:3]=1.[H-].[Na+].Br[CH2:24][C:25]1[C:26]([CH2:31]Br)=[CH:27][CH:28]=[CH:29][CH:30]=1.O>CN(C=O)C>[F:1][C:2]1[CH:20]=[CH:19][C:5]2[C:6]([CH:9]3[CH2:14][CH2:13][N:12]([CH2:15][C:16]([N:18]4[CH2:31][C:26]5[C:25](=[CH:30][CH:29]=[CH:28][CH:27]=5)[CH2:24]4)=[O:17])[CH2:11][CH2:10]3)=[N:7][O:8][C:4]=2[CH:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 66665o-Bis(bromomethyl)benzeneHCID 184673072-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]acetamide

Product 1

HCID 152856962-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]-1-(2,3-dihydro-1H-isoindol-2-yl)ethanone

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
65 °C

Procedure

To a mixture of 2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]acetamide (2.56 g, 9.2 mmol) in DMF (40 ml) was chipped in sodium hydride (770 rag, 60% in oil, 20.1 mmol) at room temperature under N2. The mixture was heated to 65° C. for 3 hours. α,α'-dibromoxylene (2.43 g, 9.2 mmol) was added and the resulting mixture was heated at 70 C. for 4 hours, then left standing overnight for 16 hours. The DMF mixture was poured into H2O (400 ml) and the organics were extracted into ethyl acetate (250 ml). The ethyl acetate solution was washed with brine and dried over MgSO4. The solvent was removed and the residue was purified by flash chromatography over a silica gel column (SiO2, 45 gm; eluted with 1% CH3OH: 99% DCM). The product thus purified as a white solid weighed 1.73 g. Recrystallization from a small amount of ethanol yielded white crystals: 1.65 g, m.p. 184°-185° C.

Workup

  1. temperaturethe resulting mixture was heated at 70 C
  2. waitleft
  3. waitstanding overnight for 16 hours
  4. extractionthe organics were extracted into ethyl acetate (250 ml)
  5. washThe ethyl acetate solution was washed with brine
  6. dry with materialdried over MgSO4
  7. customThe solvent was removed
  8. customthe residue was purified by flash chromatography over a silica gel column (SiO2, 45 gm; eluted with 1% CH3OH: 99% DCM)
  9. customThe product thus purified as a white solid
  10. customRecrystallization from a small amount of ethanol yielded white crystals

Sources & evidence

ORD record
ord-fd6c64207ca04ee3b5d10fa547c7aec5
Source dataset
uspto-grants-1996_09
Patent number
US05559117

Reaction notes

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