Potassium Carbonate → 4-(6-Fluoro-1,2-benzisoxazoi-3-yl)-1-(2'-methoxyphenyl)butylpiperidine maleate

HRID 744249Notes

Reaction equation

HRID 744249 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+].Br[CH2:24][CH2:25][CH2:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[O:34][CH3:35].[C:36]([OH:43])(=[O:42])/[CH:37]=[CH:38]\[C:39]([OH:41])=[O:40]>C(#N)C.C(O)C>[C:36]([OH:43])(=[O:42])/[CH:37]=[CH:38]\[C:39]([OH:41])=[O:40].[F:1][C:2]1[CH:16]=[CH:15][C:5]2[C:6]([CH:9]3[CH2:10][CH2:11][N:12]([CH:27]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=4[O:34][CH3:35])[CH2:26][CH2:25][CH3:24])[CH2:13][CH2:14]3)=[N:7][O:8][C:4]=2[CH:3]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 444266Maleic AcidHCID 8494213-(4-Piperidyl)-6-fluoro-1,2-benzisoxazoleHCID 190724681-(4-Bromobutyl)-2-methoxybenzene

Product 1

HCID 867482554-(6-Fluoro-1,2-benzisoxazoi-3-yl)-1-(2'-methoxyphenyl)butylpiperidine maleate

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6342AcetonitrileSolvent

Procedure

A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (2.36 g, 10.7 mmole), K2CO3 (2 g, 14.5 mmol) and 2-(4-bromobutyl)anisole (2.4 g, 10 mmol) in acetonitrile (100 ml) was heated at reflux for 2.5 hours. At the end of reaction, the solvent was removed. The residue was extracted into dichloromethane (200 ml) and filtered. The dichloromethane solution was concentrated. The crude oil obtained was purified on a flash chromatography column. The material thus purified was a light yellow oil (2.73 g, 53%). This oil was dissolved in ethanol and treated with maleic acid (607 mg, 1.0 eq) in ethanol. The 4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-(2'-methoxyphenyl)butylpiperidine maleate crystals formed on concentration and subsequent cooling to 0° C. These were collected and dried to yield 2.05 g, m.p.=132°-133° C.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 2.5 hours
  3. customAt the end of reaction
  4. customthe solvent was removed
  5. extractionThe residue was extracted into dichloromethane (200 ml)
  6. filtrationfiltered
  7. concentrationThe dichloromethane solution was concentrated
  8. customThe crude oil obtained
  9. customwas purified on a flash chromatography column
  10. customThe material thus purified
  11. dissolutionThis oil was dissolved in ethanol

Sources & evidence

ORD record
ord-e43ad2ba7e66423cb5efac38aaae598e
Source dataset
uspto-grants-1996_09
Patent number
US05559116

Reaction notes

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