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

HRID 1739304Notes

Reaction equation

HRID 1739304 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.

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-a49fa2e6f65b4bd6aba703325c69bd3c
Source dataset
uspto-grants-1999_10
Patent number
US05965546

Reaction notes

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