反应 #2271672

反应方程式

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

溶剂

acetonitrile

ethanol

反应条件

后处理

1. 1
   其他At the end of the reaction
2. 2
   其他the solvent-was removed
3. 3
   workup.DISSOLUTIONthe solids were dissolved into dichloromethane (100 ml)
4. 4
   洗涤The solution was washed with water and brine
5. 5
   干燥dried over MgSO4
6. 6
   其他prepared in the same fashion (using 0.5 g of starting material)
7. 7
   其他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)
8. 8
   workup.ADDITIONThe fractions containing the pure product
9. 9
   浓缩concentrated down to a light oil (3.68 g)

实验过程

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.

来源