反応 #2298663

反応方程式

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

K2CO3

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

fumaric acid

→

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

溶媒

dimethylformamide

acetonitrile

ethanol

ethanol

反応条件

後処理

1. 1
   その他At the end of the reaction
2. 2
   濃縮the solvent was concentrated down to about 30 ml
3. 3
   その他partitioned between water (200 ml) and dichloromethane (300 ml)
4. 4
   その他The dichloromethane solution was separated
5. 5
   洗浄washed with water and brine
6. 6
   乾燥dried over MgSO4
7. 7
   その他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
   その他The material thus obtained

実験手順

A stirred mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole hydrochloride (3.0 g; 11.7 mmoles), K2CO3 (3.0 g), 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 hr. 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-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methylphenyl]ethanone hemifumarate crystals formed on cooling at 0° C. This was collected and weighed 1.5 g, m.p.=185°-187° C.

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