Reaktion #2271672

Reaktionsgleichung

K2CO3

3-(2-methoxyphenoxy)propyl chloride

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

fumaric acid

→

6-fluoro-3-[1-[3-(2-methoxyphenoxy)-propyl)-4-piperidinyl]-1,2-benzisoxazole fumarate

Lösungsmittel

acetonitrile

ethanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeAt the end of the reaction
2. 2
   Sonstigethe solvent-was removed
3. 3
   workup.DISSOLUTIONthe solids were dissolved into dichloromethane (100 ml)
4. 4
   WaschenThe solution was washed with water and brine
5. 5
   Trocknendried over MgSO4
6. 6
   Sonstigeprepared in the same fashion (using 0.5 g of starting material)
7. 7
   SonstigeThe combined material was purified by flash chromatography on a silica gel column (49 g, eluted with 0.5% diethylamine: 1% methanol:98.5% dichloromethane, 1 L)
8. 8
   workup.ADDITIONThe fractions containing the pure product
9. 9
   Einengenconcentrated down to a light oil (3.68 g)

Vorschrift

A stirred mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (2.45 g: 11.1 mmol). K2CO3 (2.0 g), and 3-(2-methoxyphenoxy)propyl chloride (3.5 g, 17.4 mmol) in acetonitrile (40 ml) was heated at 90° C. for 4 hours. At the end of the reaction, the solvent-was removed, and the solids were dissolved into dichloromethane (100 ml). The solution was washed with water and brine, then dried over MgSO4. The crude material from the solution was combined with 1.2 g of crude material prepared in the same fashion (using 0.5 g of starting material). The combined material was purified by flash chromatography on a silica gel column (49 g, eluted with 0.5% diethylamine: 1% methanol:98.5% dichloromethane, 1 L). The fractions containing the pure product were pooled and concentrated down to a light oil (3.68 g). This oil was treated with fumaric acid (1.14 g, 9.8 mmol) in ethanol (13 ml). The 6-fluoro-3-[1-[3-(2-methoxyphenoxy)-propyl)-4-piperidinyl]-1,2-benzisoxazole fumarate crystals obtained weighed 4.01 g (60%), m.p.=169°-170° C.

Quelle