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

HRID 1955928Notes

Reaction equation

HRID 1955928 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.Br[CH2:22][C:23]1[C:24]([CH2:29]Br)=[CH:25][CH:26]=[CH:27][CH:28]=1.O>CN(C=O)C.[H-].[Na+]>[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[CH2:29][C:24]5[C:23](=[CH:28][CH:27]=[CH:26][CH:25]=5)[CH2:22]4)=[O:17])[CH2:11][CH2:10]3)=[N:7][O:8][C:4]=2[CH:3]=1

Participants

6

Reactant 3

HCID 962WaterHCID 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 2

HCID 6228DimethylformamideSolvent2×HCID 24758Sodium hydrideSolvent

Conditions

Temperature
70 °C

Procedure

To a mixture of 2-[4(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]acetamide 21 (2.56 g, 9.2 mmol) in DMF (40 ml) was chipped in sodium hydride (770 mg, 60% in oil, 20.1 ml mol) at room temperature under N2. The mixture was heated to 65 C for 3 hours. α,α'-dibromoxylene (2.43 g, 9.2 inmol) 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 . m.p. 184°-185° C.

Workup

  1. temperatureThe mixture was heated to 65 C for 3 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-4048b72f2c6d4ab3b36108f06455206d
Source dataset
uspto-grants-1998_07
Patent number
US05776963

Reaction notes

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