Reaction #2271673

Reaction equation

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

K2CO3

1-[3-(3-chloropropoxy)-4-methoxy-phenyl]phenylmethanone

→

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

Solvents

acetonitrile

Conditions

Workup

1. 1
   Temperatureat reflux for 4 hours
2. 2
   OtherAt the end of the reaction
3. 3
   Otherthe solvent was evaporated
4. 4
   Otherthe residue was partitioned between water (150 ml) and dichloromethane (400 ml)
5. 5
   WashThe dichloromethane solution was washed with water and brine (100 ml)
6. 6
   Dryingdried over MgSO4
7. 7
   Concentrationconcentrated to an oil
8. 8
   OtherThe purification
9. 9
   Washwas done by flash chromatography over a silica gel column (SiO2: 40 g; eluted with dichloromethane, 300 ml: 1% methanol in dichloromethane, 850 ml)
10. 10
    OtherThe material thus obtained as a colorless oil
11. 11
    OtherRecrystallization from ethanol (150 ml)

Procedure

A stirred mixture of 6-fluoro-3-(4-piperidinyl)-1,2 benzisoxazole (2.01 g: 9.13 mmol). K2CO3 (2.0 g) and 1-[3-(3-chloropropoxy)-4-methoxy-phenyl]phenylmethanone (3.93 g; 11.3 mmol) and acetonitrile (50 ml) was heated at reflux for 4 hours. At the end of the reaction, the solvent was evaporated and the residue was partitioned between water (150 ml) and dichloromethane (400 ml). The dichloromethane solution was washed with water and brine (100 ml), dried over MgSO4, then concentrated to an oil. The purification was done by flash chromatography over a silica gel column (SiO2: 40 g; eluted with dichloromethane, 300 ml: 1% methanol in dichloromethane, 850 ml). The material thus obtained as a colorless oil solidified on standing. Recrystallization from ethanol (150 ml) gave 1-[3-[3-[4-(6- fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-4-methoxyphenyl]phenylmethanone as white crystals. 3.07 g (63%), mp=140°-141° C.

Source