반응 #83910

반응 방정식

(2,4-difluorophenyl)[1-(phenylmethyl)-3-pyrrolidinyl]methanone oxime

potassium hydroxide

water

fumaric acid

→

6-fluoro-3-[1-(phenylmethyl)-3-pyrrolidinyl]-1,2-benzisoxazole fumarate

수율 74.8%

용매

ethanol

ethanol

ethanol

반응 조건

후처리

1. 1
   온도was heated
2. 2
   온도at reflux for 2 hours
3. 3
   기타At the end of the reaction
4. 4
   온도the solution was cooled
5. 5
   기타ethanol was removed on a rotary evaporator
6. 6
   workup.ADDITIONThe aqueous mixture was diluted with water (100 ml)
7. 7
   추출then extracted with dichloromethane (500 ml)
8. 8
   세척The organic solution was washed with brine
9. 9
   건조dried over anhydrous MgSO4
10. 10
    농축The solution was concentrated to an oil (9.8 g)
11. 11
    기타The crude product was purified by flash chromatography over a silica gel column
12. 12
    기타The product thus obtained
13. 13
    기타Crystallization
14. 14
    workup.ADDITIONslowly with the addition of isopropyl ether
15. 15
    기타Recrystallization from ethanol (15 ml)

실험 절차

A mixture of (2,4-difluorophenyl)[1-(phenylmethyl)-3-pyrrolidinyl]methanone oxime (10.8 g, 34.2 mmol), potassium hydroxide (10 g), water (100 ml), and ethanol (100 ml) was heated at reflux for 2 hours. At the end of the reaction, the solution was cooled and ethanol was removed on a rotary evaporator. The aqueous mixture was diluted with water (100 ml) then extracted with dichloromethane (500 ml). The organic solution was washed with brine and dried over anhydrous MgSO4. The solution was concentrated to an oil (9.8 g). The crude product was purified by flash chromatography over a silica gel column. The product thus obtained weighed 4.46 g (44%) as a light yellow oil. The oily product was dissolved in ethanol, and then treated with a solution of fumaric acid (1.73 g, 1.0 eq) in ethanol. Crystallization took place slowly with the addition of isopropyl ether. Recrystallization from ethanol (15 ml) gave 4.6 g of 6-fluoro-3-[1-(phenylmethyl)-3-pyrrolidinyl]-1,2-benzisoxazole fumarate as white crystals, m.p.=142°-144° C.

출처