Reaction #83947

Reaction equation

4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidine

K2CO3

epibromohydrin

→

white crystals

Yield 33.3%

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

Yield 33.3%

Solvents

acetonitrile

Conditions

Workup

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

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.

Source