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

HRID 1450810Notes

Reaction equation

HRID 1450810 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-2f29bade4a5a4f9eb0e87e7e4ae88c01
Source dataset
uspto-grants-1997_02
Patent number
US05602159

Reaction notes

Loading…