Potassium Carbonate → 2-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]methyl-1,4-benzodioxan

HRID 264185Notes

Reaction equation

HRID 264185 reaction equation
[F:1][C:2]1[CH:16]=[CH:15][C:5]2[C:6]([CH:9]3[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]3)=[N:7][O:8][C:4]=2[CH:3]=1.C([O-])([O-])=O.[K+].[K+].CS(O[CH2:28][CH:29]1[O:34][C:33]2[CH:35]=[CH:36][CH:37]=[CH:38][C:32]=2[O:31][CH2:30]1)(=O)=O>C(#N)C>[F:1][C:2]1[CH:16]=[CH:15][C:5]2[C:6]([CH:9]3[CH2:10][CH2:11][N:12]([CH2:28][CH:29]4[O:34][C:33]5[CH:35]=[CH:36][CH:37]=[CH:38][C:32]=5[O:31][CH2:30]4)[CH2:13][CH2:14]3)=[N:7][O:8][C:4]=2[CH:3]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 2634452,3-Dihydro-1,4-benzodioxin-2-ylmethyl methanesulfonateHCID 8494213-(4-Piperidyl)-6-fluoro-1,2-benzisoxazole

Product 1

HCID 153849682-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]methyl-1,4-benzodioxan

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A stirred mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (3.0 g, 13.6 mmol), K2CO3 (2.45 g, 17.7 mmol), 2-methanesulfonyloxymethyl-1,4-benzodioxan (3.35 g, 13.7 mmole) in acetonitrile (100 ml) was heated at reflux for 12 hours. At the end of the reaction, the insolubles were filtered and rinsed with dichloromethane. The organic solution was concentrated. The crude oil was purified by flash chromatography on a silica gel column. The fractions containing the pure product were pooled and concentrated to a light yellow oil (3.94 g, 74%). Crystallization from ethanol and petroleum ether gave 2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]methyl-1,4-benzodioxan as off-white crystals, 2.22 g, m.p.=86°-87° C.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 12 hours
  3. customAt the end of the reaction
  4. filtrationthe insolubles were filtered
  5. washrinsed with dichloromethane
  6. concentrationThe organic solution was concentrated
  7. customThe crude oil was purified by flash chromatography on a silica gel column
  8. additionThe fractions containing the pure product
  9. concentrationconcentrated to a light yellow oil (3.94 g, 74%)
  10. customCrystallization from ethanol and petroleum ether

Sources & evidence

ORD record
ord-71178cbf502b480a8336d361650528e3
Source dataset
uspto-grants-1997_07
Patent number
US05646161

Reaction notes

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