Reaction #2271683

Reaction equation

acetonitrile

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

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

K2CO3

→

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

Yield 56.0%

Solvents

water

Conditions

Workup

1. 1
   Temperaturerefluxed for 16 hours
2. 2
   TemperatureAfter cooling
3. 3
   Extractionthe aqueous mixture extracted with ethyl acetate
4. 4
   WashThe extract was washed (H2O)
5. 5
   Dryingdried (MgSO4)
6. 6
   Concentrationthe solvent was concentrated to an oil, which upon evacuation at high vacuum
7. 7
   Otherafforded 3.2 g of a waxy solid
8. 8
   OtherThe solid was chromatographed on a Waters preparative LC (silica columns, eluting with methanol-dichloromethane)

Procedure

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). Kl (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 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-trifluoroethanone solid, m.p.=94°-96° C.

Source