Reaktion #83910

Reaktionsgleichung

(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

Ausbeute 74.8%

Lösungsmittel

ethanol

ethanol

ethanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturwas heated
2. 2
   Temperaturat reflux for 2 hours
3. 3
   SonstigeAt the end of the reaction
4. 4
   Temperaturthe solution was cooled
5. 5
   Sonstigeethanol was removed on a rotary evaporator
6. 6
   workup.ADDITIONThe aqueous mixture was diluted with water (100 ml)
7. 7
   Extraktionthen extracted with dichloromethane (500 ml)
8. 8
   WaschenThe organic solution was washed with brine
9. 9
   Trocknendried over anhydrous MgSO4
10. 10
    EinengenThe solution was concentrated to an oil (9.8 g)
11. 11
    SonstigeThe crude product was purified by flash chromatography over a silica gel column
12. 12
    SonstigeThe product thus obtained
13. 13
    SonstigeCrystallization
14. 14
    workup.ADDITIONslowly with the addition of isopropyl ether
15. 15
    SonstigeRecrystallization from ethanol (15 ml)

Vorschrift

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.

Quelle