Reaction #2271670

Reaction equation

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

K2CO3

1-[4-(4-bromobutoxy)-3-methoxyphenyl]ethanone

dimethylformamide

→

product

Yield 87.4%

1-[4-[4-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]butoxy]-3-methoxyphenyl]ethanone

Yield 87.4%

Solvents

water

Conditions

Workup

1. 1
   Extractionthe aqueous mixture was extracted with ethyl acetate
2. 2
   WashThe ethyl acetate was washed (water)
3. 3
   Dryingdried (MgSO4)
4. 4
   Concentrationthe solvent was concentrated
5. 5
   Otherto yield initially an oil, which
6. 6
   OtherThe solid was triturated with hexane
7. 7
   Othercollected

Procedure

A stirred mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole hydrochloride (5.1 g, 0.02 mol). K2CO3 (5.2 g, 0.04 mol), 1-[4-(4-bromobutoxy)-3-methoxyphenyl]ethanone (6.6 g, 22 mmol), and dimethylformamide (60 ml) was heated a 75° C. for 5 hours. The reaction was poured into water, and the aqueous mixture was extracted with ethyl acetate. The ethyl acetate was washed (water), dried (MgSO4), and the solvent was concentrated to yield initially an oil, which solidified upon standing. The solid was triturated with hexane and collected to afford 7.7 g of the product as a waxy solid. The compound was chromatographed on a Waters Prep 500 utilizing silica gel columns and eluting with dichloromethane/methanol (5%). Concentration of the appropriate fractions yielded 5.1 g of off-white solid 1-[4-[4-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]-butoxy]-3-methoxyphenyl]ethanone, which when recrystallized from ethyl alcohol yielded 3.2 g. (36%) of feathery white needles, m.p.=88°-90° C.

Source