反应 #2271679

反应方程式

fumaric acid

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

K2CO3

1-[4-(3-bromopropoxy)-3-methylphenyl]ethanone

→

1-[4-[3-[4-(6-fluoro-1,2-benzisoxazole-3-yl)-1-piperidinyl]propoxy]-3-methylpheny]ethanone hemifumarate

溶剂

ethanol

ethanol

dimethylformamide

acetonitrile

反应条件

后处理

1. 1
   其他At the end of the reaction
2. 2
   浓缩the solvent was concentrated down to about 30 ml
3. 3
   其他partitioned between water (200 ml) and dichloromethane (300 ml)
4. 4
   其他The dichloromethane solution was separated
5. 5
   洗涤washed with water and brine
6. 6
   干燥dried over MgSO4
7. 7
   其他The crude product from the evaporated solution was purified by flash chromatography over a silica gel column (SiO2, 60 g, eluted with 1% methanol in dichloromethane, 600 ml; 2% methanol in dichloromethane, 600 ml)
8. 8
   其他The material thus obtained

实验过程

A stirred mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole hydrochloride (3.0 g; 11.7 mmol). K2CO3 (3.0g), and 1-[4-(3-bromopropoxy)-3-methylphenyl]ethanone (3.19 g) in dimethylformamide (20 ml) and acetonitrile (50 ml) was heated at 95° C. for 4 hours. At the end of the reaction, the solvent was concentrated down to about 30 ml, then partitioned between water (200 ml) and dichloromethane (300 ml). The dichloromethane solution was separated and washed with water and brine, then dried over MgSO4. The crude product from the evaporated solution was purified by flash chromatography over a silica gel column (SiO2, 60 g, eluted with 1% methanol in dichloromethane, 600 ml; 2% methanol in dichloromethane, 600 ml). The material thus obtained was a light yellow oil, weight: 2.07 g (43%). This oil was dissolved in ethanol and treated with a solution of fumaric acid (585 mg) in ethanol. The 1-[4-[3-[4-(6-fluoro-1,2-benzisoxazole-3-yl)-1-piperidinyl]propoxy]-3-methylpheny]ethanone hemifumarate crystals formed on cooling at 0° C. This was collected and weighed 1.5 g., m.p.=185°-187° C.

来源