反应详情

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.

1. temperaturewas heated
2. temperatureat reflux for 2 hours
3. customAt the end of the reaction
4. temperaturethe solution was cooled
5. customethanol was removed on a rotary evaporator
6. additionThe aqueous mixture was diluted with water (100 ml)
7. extractionthen extracted with dichloromethane (500 ml)
8. washThe organic solution was washed with brine
9. dry with materialdried over anhydrous MgSO4
10. concentrationThe solution was concentrated to an oil (9.8 g)
11. customThe crude product was purified by flash chromatography over a silica gel column
12. customThe product thus obtained
13. customCrystallization
14. additionslowly with the addition of isopropyl ether
15. customRecrystallization from ethanol (15 ml)