Reacción #2271677

Ecuación de reacción

fumaric acid

N-[3-(bromopropoxy)-4-methoxyphenyl]acetamide

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

K2CO3

→

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

Disolventes

ethanol

ethanol

dimethylformamide

acetonitrile

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroAt the end of the reaction
2. 2
   Concentraciónthe solvent was concentrated
3. 3
   Extracciónthe mixture was extracted into dichloromethane (500 ml)
4. 4
   LavadoThe organic solution was washed with water (500 ml) and brine (400 ml)
5. 5
   Otrodried
6. 6
   Concentraciónconcentrated to a crude oil
7. 7
   OtroThe purification
8. 8
   Lavadowas effected by flash chromatography over a silica gel column (SiO2, 65 g, eluted with 1% CH3OH:dichloromethane, 1.2 l; and 3% CH3OH:dichloromethane, 500 ml)
9. 9
   OtroThe material thus obtained

Procedimiento

A mixture of 6fluoro-3-(4-piperidinyl)-1,2-benzisoxazole hydrochloride (3.94 g: 15.4 mmol) K2CO3 (3.67 g. 26.6 mmole). N-[3-(bromopropoxy)-4-methoxyphenyl]acetamide (5.56 g, 18.6 mmol) in dimethylformamide (75 ml) and acetonitrile (100 ml) was heated at 100° C. for 3 hours. At the end of the reaction, the solvent was concentrated and the mixture was extracted into dichloromethane (500 ml). The organic solution was washed with water (500 ml) and brine (400 ml), dried, then concentrated to a crude oil. The purification was effected by flash chromatography over a silica gel column (SiO2, 65 g, eluted with 1% CH3OH:dichloromethane, 1.2 l; and 3% CH3OH:dichloromethane, 500 ml). The material thus obtained weighed 2.33 g (34.3%) as in oil. This material was dissolved in ethanol and treated with a solution of fumaric acid (661 mg) in ethanol. The N-[3-[3-[4(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-4-methoxyphenyl]acetamide hemifumarate was obtained as off-white crystals weighing 2.17 g, m.p.=205-206° C.

Fuente