반응 #2271677

반응 방정식

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

용매

ethanol

ethanol

dimethylformamide

acetonitrile

반응 조건

후처리

1. 1
   기타At the end of the reaction
2. 2
   농축the solvent was concentrated
3. 3
   추출the mixture was extracted into dichloromethane (500 ml)
4. 4
   세척The organic solution was washed with water (500 ml) and brine (400 ml)
5. 5
   기타dried
6. 6
   농축concentrated to a crude oil
7. 7
   기타The purification
8. 8
   세척was 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
   기타The material thus obtained

실험 절차

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.

출처