반응 #83852

반응 방정식

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

K2CO3

3-(2-methoxyphenoxy)propyl chloride

fumaric acid

→

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

용매

acetonitrile

ethanol

반응 조건

후처리

1. 1
   기타At the end of the reaction
2. 2
   기타the solvent was removed
3. 3
   workup.DISSOLUTIONthe solids were dissolved into dichloromethane (100 ml)
4. 4
   세척The solution was washed with water and brine
5. 5
   건조dried over MgSO4
6. 6
   기타prepared in the same fashion (using 0.5 g of starting material)
7. 7
   기타The 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
   농축concentrated down to a light oil (3.68 g)

실험 절차

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.

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