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

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.

1. temperatureThe mixture was heated to 65 C for 3 hours
2. temperaturethe resulting mixture was heated at 70 C for 4 hours
3. waitleft
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

ORD record

ord-d2b79237c6a24c4c89f876cea0f630ec

Source dataset

uspto-grants-1997_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05614543