反応 #2271680

反応方程式

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

K2CO3

4-(3-bromopropoxy)-3-methoxybenzonitrile

→

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

収率 68.2%

溶媒

acetonitrile

反応条件

後処理

1. 1
   温度at reflux for 3 hours
2. 2
   その他At the end of the reaction
3. 3
   その他the solvent was removed on a rotary evaporator
4. 4
   抽出The organic material was extracted into dichloromethane (250 ml)
5. 5
   ろ過the inorganics were filtered off
6. 6
   濃縮The dichloromethane solution was concentrated to a crude oil
7. 7
   その他The purification
8. 8
   洗浄was done by flash chromatography over a silica gel column (SiO2, 55 g: eluted with dichloromethane, 600 ml; 1% methanol in dichloromethane, 600 ml)
9. 9
   その他The material thus obtained
10. 10
    その他was crystallized from a small amount of dichloromethane
11. 11
    その他Recrystallization from ethanol (25 ml)

実験手順

A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (3.0 g, 13.6 mmol). K2CO3 (2.8 g), 4-(3-bromopropoxy)-3-methoxybenzonitrile (4.0 g, 14.8 mmol) in acetonitrile (70 ml) was heated at reflux for 3 hours. At the end of the reaction, the solvent was removed on a rotary evaporator. The organic material was extracted into dichloromethane (250 ml) and the inorganics were filtered off. The dichloromethane solution was concentrated to a crude oil. The purification was done by flash chromatography over a silica gel column (SiO2, 55 g: eluted with dichloromethane, 600 ml; 1% methanol in dichloromethane, 600 ml). The material thus obtained was crystallized from a small amount of dichloromethane. Recrystallization from ethanol (25 ml) provided 3.8 g (68%) of 4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxybenzonitrile as white crystals, m.p.=107°-108° C.

出典