反应 #2271677

反应方程式

fumaric acid

N-[3-(bromopropoxy)-4-methoxyphenyl]acetamide

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

K2CO3

→

N-[3-[3-[4(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-4-methoxyphenyl]acetamide 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
3. 3
   萃取the mixture was extracted into dichloromethane (500 ml)
4. 4
   洗涤The organic solution was washed with water (500 ml) and brine (400 ml)
5. 5
   其他dried
6. 6
   浓缩concentrated to a crude oil
7. 7
   其他The purification
8. 8
   洗涤was effected by flash chromatography over a silica gel column (SiO2, 65 g, eluted with 1% CH3OH:dichloromethane, 1.2 l; and 3% CH3OH:dichloromethane, 500 ml)
9. 9
   其他The material thus obtained

实验过程

A mixture of 6fluoro-3-(4-piperidinyl)-1,2-benzisoxazole hydrochloride (3.94 g: 15.4 mmol) K2CO3 (3.67 g. 26.6 mmole). N-[3-(bromopropoxy)-4-methoxyphenyl]acetamide (5.56 g, 18.6 mmol) in dimethylformamide (75 ml) and acetonitrile (100 ml) was heated at 100° C. for 3 hours. At the end of the reaction, the solvent was concentrated and the mixture was extracted into dichloromethane (500 ml). The organic solution was washed with water (500 ml) and brine (400 ml), dried, then concentrated to a crude oil. The purification was effected by flash chromatography over a silica gel column (SiO2, 65 g, eluted with 1% CH3OH:dichloromethane, 1.2 l; and 3% CH3OH:dichloromethane, 500 ml). The material thus obtained weighed 2.33 g (34.3%) as in oil. This material was dissolved in ethanol and treated with a solution of fumaric acid (661 mg) in ethanol. The N-[3-[3-[4(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-4-methoxyphenyl]acetamide hemifumarate was obtained as off-white crystals weighing 2.17 g, m.p.=205-206° C.

来源