反应详情

A solution of (E)-N-(2-(6-bromobenzo[d]isoxazol-3-yl)benzylidene)-1,1-bis(4-fluorophenyl)methanamine (Compound 8) (1.34 g) in dry tetrahydrofuran (15 mL) under nitrogen was cooled to −78° C. with stirring and a 1M solution of potassium tert-butoxide in tetrahydrofuran (3.2 mL) added dropwise. Solution turned dark purple. After 20 min (iodomethyl)cyclopropane (1.45 g) was added in one portion and solution slowly warmed to room temperature, stirred at this temperature for 1.5 h then quenched by the addition of water (10 mL) and extracted with ethyl acetate. The organic extract was dried over anhydrous magnesium sulfate and evaporated to leave a dark red gum that was dissolved in acetone (20 mL) and an aqueous 2N HCl solution (15 mL) added and the mixture stirred overnight. The acetone was removed by evaporation and the aqueous solution extracted with dichloromethane. The aqueous solution was made basic with sodium bicarbonate and extracted with dichloromethane, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. SCX purification (eluting with methanol then ammonia in methanol) followed by flash chromatography on silica eluting with 0 to 5% methanol in dichloromethane gave the title product (0.39 g).

1. stirringstirred at this temperature for 1.5 h
2. customthen quenched by the addition of water (10 mL)
3. extractionextracted with ethyl acetate
4. extractionThe organic extract
5. dry with materialwas dried over anhydrous magnesium sulfate
6. customevaporated
7. customto leave a dark red gum that
8. stirringthe mixture stirred overnight
9. customThe acetone was removed by evaporation
10. extractionthe aqueous solution extracted with dichloromethane
11. extractionextracted with dichloromethane
12. dry with materialdried over anhydrous magnesium sulfate
13. customevaporated under reduced pressure
14. customSCX purification (
15. washeluting with methanol