Reaktion #83922

Reaktionsgleichung

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

N-(3-chloropropyl)piperidine hydrochloride

K2CO3

water

→

white crystals

4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-[3-(1-piperidinyl)propyl]piperidine difumarate

Lösungsmittel

acetonitrile

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturwas heated
2. 2
   Temperaturat reflux for 16 hours
3. 3
   WaschenThe mixture was washed with brine
4. 4
   Sonstigethe layers were separated
5. 5
   EinengenThe organic solution was concentrated
6. 6
   SonstigeThe crude product (6.4 g) was purified by flash chromatography over a silica gel column (55 g, sorbsil C-30; eluted with 2% CH3OH:0.5% DEA in DCM, 1.4 l)
7. 7
   SonstigeThe oil thus purified (4.5 g)
8. 8
   workup.ADDITIONwas treated with fumaric acid (1.6 g) in ethanol
9. 9
   SonstigeThe solid was collected
10. 10
    SonstigeRecrystallization from ethanol

Vorschrift

A mixture of 4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidine (3.0 g, 13.6 mmol), N-(3-chloropropyl)piperidine hydrochloride (4.05 g, 20.4 mmol), K2CO3 (6 g, 43.4 mmol), tetrabutylammonium hydrogen sulfate (phase transfer catalyst, 2.3 g) in acetonitrile (100 ml) and water (15 ml) was heated at reflux for 16 hours. The mixture was washed with brine and the layers were separated. The organic solution was concentrated. The crude product (6.4 g) was purified by flash chromatography over a silica gel column (55 g, sorbsil C-30; eluted with 2% CH3OH:0.5% DEA in DCM, 1.4 l). The oil thus purified (4.5 g) was treated with fumaric acid (1.6 g) in ethanol. The solid was collected: weight 3.1 g, m.p.178°-181° C. Recrystallization from ethanol yielded 2.28 g of white crystals, m.p.=190°-192° C.

Quelle