تفاعل #2271677

معادلة التفاعل

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

المذيبات

ethanol

ethanol

dimethylformamide

acetonitrile

ظروف التفاعل

المعالجة

1. 1
   أخرىAt the end of the reaction
2. 2
   تركيزthe solvent was concentrated
3. 3
   استخلاصthe mixture was extracted into dichloromethane (500 ml)
4. 4
   غسيلThe organic solution was washed with water (500 ml) and brine (400 ml)
5. 5
   أخرىdried
6. 6
   تركيزconcentrated to a crude oil
7. 7
   أخرىThe purification
8. 8
   غسيلwas 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
   أخرىThe material thus obtained

الإجراء التجريبي

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.

المصدر