Potassium Carbonate → N-[2,3-Epoxypropyl)-4-(6fluoro-1,2-benzisoxazol-3-yl)piperidine fumarate

HRID 1449958Notes

Reaction equation

HRID 1449958 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:17]([O-:20])([O-:19])=O.[K+].[K+].[CH2:23]([CH:25]1[O:27][CH2:26]1)Br>C(#N)C>[C:4]([OH:27])(=[O:8])/[CH:5]=[CH:15]/[C:17]([OH:20])=[O:19].[O:27]1[CH2:26][CH:25]1[CH2:23][N:12]1[CH2:11][CH2:10][CH:9]([C:6]2[C:5]3[CH:15]=[CH:16][C:2]([F:1])=[CH:3][C:4]=3[O:8][N:7]=2)[CH2:14][CH2:13]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 18430EpibromohydrinHCID 8494213-(4-Piperidyl)-6-fluoro-1,2-benzisoxazole

Product 1

HCID 18467317N-[2,3-Epoxypropyl)-4-(6fluoro-1,2-benzisoxazol-3-yl)piperidine fumarateYield 33.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidine (11 g, 50 mmol), K2CO3 (7.5 g, 54 mmol) and epibromohydrin (9 g, 54 mmol) in acetonitrile (150 ml) was heated at reflux for 16 hours. The mixture was filtered and concentrated to dryness. The crude product was purified by flash chromatography (SiO2, 180 g, eluted with methylene chloride (DCM), and 1-2% CH3OH in DCM). The material thus purified as off-white solids weighed 8.7 g (63%). This material (3 g) was converted to fumarate salt in ethanol and isopropyl ether to give 3.27 g Of white crystals, m.p.=145°-147° C. ANALYSIS: Calculated for C15H17FN2O2.C4H4O4 : 58.16%C 5.39%H 7.14%N Found: 57.93%C 5.35%H 7.02%N

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 16 hours
  3. filtrationThe mixture was filtered
  4. concentrationconcentrated to dryness
  5. customThe crude product was purified by flash chromatography (SiO2, 180 g, eluted with methylene chloride (DCM), and 1-2% CH3OH in DCM)
  6. customThe material thus purified as off-white solids

Sources & evidence

ORD record
ord-0857fbf2934c4f7e872622922c065b2d
Source dataset
uspto-grants-1997_02
Patent number
US05599821

Reaction notes

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