Reaktion #83871

Reaktionsgleichung

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

K2CO3

1-[4-(3-chloropropoxy)-3-(methylamino)phenyl]ethanone

acetonitrile

→

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

Ausbeute 47.9%

Lösungsmittel

water

methanol methylene chloride

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturat reflux under nitrogen for 23 hours
2. 2
   Extraktionthe aqueous mixture was extracted with ethyl acetate
3. 3
   ExtraktionThe ethyl acetate extract
4. 4
   Waschenwas washed twice with water
5. 5
   Trocknendried with MgSO4
6. 6
   Einengenwas concentrated
7. 7
   Sonstigeto yield 4.8 g of a damp, brown solid
8. 8
   SonstigeConcentration of appropriate fractions afforded 2.4 g
9. 9
   SonstigeRecrystallization from ethanol

Vorschrift

A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (2.3 g, 10.3 mmol), K2CO3 (1.4 g, 10.3 mmol), 1-[4-(3-chloropropoxy)-3-(methylamino)phenyl]ethanone (2.5 g, 10.3 mmol), KI (0.10 g), and acetonitrile (100 ml) was stirred at reflux under nitrogen for 23 hours. The reaction was cooled to ambient temperature, poured into water, and the aqueous mixture was extracted with ethyl acetate. The ethyl acetate extract was washed twice with water, dried with MgSO4 and was concentrated to yield 4.8 g of a damp, brown solid. The compound was isolated by preparative HPLC (Waters Associates prep LC/System 500, utilizing 2 silica gel columns and 4% methanol-methylene chloride as eluent). Concentration of appropriate fractions afforded 2.4 g. Recrystallization from ethanol gave 2.1 g of 1-[4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-(methylamino)phenyl]ethanone as a beige solid, m.p.=151°-153° C.

Quelle