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

HRID 2184596Notes

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

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. ANALYSIS: Calculated for C22H22FN3O2: 69.64%C 5.84%H 11.07%N Found: 69.48%C 5.67%H 11.05%N

Workup

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

Sources & evidence

ORD record: ord-5ec6e2f13cff41a6bf441d3c341d383b
Source dataset: uspto-grants-2002_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: USRE037729E1

Reaction notes

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