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

HRID 235483Notes

Reaction equation

HRID 235483 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 mg, 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. for 4 hours
  2. waitleft
  3. extractionthe organics were extracted into ethyl acetate (250 ml)
  4. washThe ethyl acetate solution was washed with brine
  5. dry with materialdried over MgSO4
  6. customThe solvent was removed
  7. customthe residue was purified by flash chromatography over a silica gel column (SiO2, 45 gm; eluted with 1% CH3OH: 99% DCM)
  8. customThe product thus purified as a white solid
  9. customRecrystallization from a small amount of ethanol yielded white crystals

Sources & evidence

ORD record
ord-3bf66a5d903d4a34b3701b6b4d354c41
Source dataset
uspto-grants-1997_01
Patent number
US05597842

Reaction notes

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