Reaktion #83864

Reaktionsgleichung

6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole

1-[4-(3-chloropropoxy)-3-methoxyphenyl]-2,2,2-trifluoroethanone

K2CO3

acetonitrile

→

1-[4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]-propoxy]-3-methoxyphenyl]-2,2,2-trifluoro-ethanone

Ausbeute 56.0%

Lösungsmittel

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturrefluxed for 16 hours
2. 2
   TemperaturAfter cooling
3. 3
   Extraktionthe aqueous mixture extracted with ethyl acetate
4. 4
   WaschenThe extract was washed (H2O)
5. 5
   Trocknendried (MgSO4)
6. 6
   Einengenthe solvent was concentrated to an oil, which upon evacuation at high vacuum
7. 7
   Sonstigeafforded 3.2 g of a waxy solid
8. 8
   SonstigeThe solid was chromatographed on a Waters preparative LC (silica columns, eluting with 3% methanol-dichloromethane)

Vorschrift

A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (1.5 g, 6.7 mmol), 1-[4-(3-chloropropoxy)-3-methoxyphenyl]-2,2,2-trifluoroethanone (2.0 g, 6.7 mmol), K2CO3 (0.88 g), KI (0.1 g) and acetonitrile (50 ml) was stirred and refluxed for 16 hours. After cooling, the reaction was poured into water and the aqueous mixture extracted with ethyl acetate. The extract was washed (H2O), dried (MgSO4), and the solvent was concentrated to an oil, which upon evacuation at high vacuum afforded 3.2 g of a waxy solid. The solid was chromatographed on a Waters preparative LC (silica columns, eluting with 3% methanol-dichloromethane). Concentration of the appropriate fractions gave 1.8 g (56%) of 1-[4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]-propoxy]-3-methoxyphenyl]-2,2,2-trifluoro-ethanone solid, m.p.=94°-96° C.

Quelle