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

HRID 977698Notes

Reaction equation

HRID 977698 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-72629cd59843430db9381b974f33849c
Source dataset
uspto-grants-1997_03
Patent number
US05614543

Reaction notes

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