Reaktion #2271677

Reaktionsgleichung

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

Lösungsmittel

ethanol

ethanol

dimethylformamide

acetonitrile

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeAt the end of the reaction
2. 2
   Einengenthe solvent was concentrated
3. 3
   Extraktionthe mixture was extracted into dichloromethane (500 ml)
4. 4
   WaschenThe organic solution was washed with water (500 ml) and brine (400 ml)
5. 5
   Sonstigedried
6. 6
   Einengenconcentrated to a crude oil
7. 7
   SonstigeThe purification
8. 8
   Waschenwas 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
   SonstigeThe material thus obtained

Vorschrift

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.

Quelle