反応 #320326

反応方程式

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

K2CO3

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

fumaric acid

→

N-[3-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-4-methoxyphenyl]acetamide 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
3. 3
   抽出the mixture was extracted into dichloromethane (500 ml)
4. 4
   洗浄The organic solution was washed with water (500 ml) and brine (400 ml)
5. 5
   その他dried
6. 6
   濃縮concentrated to a crude oil
7. 7
   その他The purification
8. 8
   洗浄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
   その他The material thus obtained

実験手順

A mixture of 6-fluoro-3-(4-piperidinyl)-l,2-benzisoxazole hydrochloride (3.94 g, 15.4 mmol), K2CO3 (3.67 g, 26.6 mmole), N-[3-(3-bromopropoxy)-4methoxyphenyl]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 an 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.

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