반응 #562614

반응 방정식

HCl

(E)-N-(2-(6-bromobenzo[d]isoxazol-3-yl)benzylidene)-1,1-bis(4-fluorophenyl)methanamine

Compound 8

(E)-N-(2-(6-bromobenzo[d]isoxazol-3-yl)benzylidene)-1,1-bis(4-fluorophenyl)methanamine

potassium tert-butoxide

(iodomethyl)cyclopropane

→

title product

수율 41.0%

1-(2-(6-bromobenzo[d]isoxazol-3-yl)phenyl)-2-cyclopropylethanamine

수율 41.0%

용매

tetrahydrofuran

tetrahydrofuran

acetone

반응 조건

후처리

1. 1
   workup.STIRRINGstirred at this temperature for 1.5 h
2. 2
   기타then quenched by the addition of water (10 mL)
3. 3
   추출extracted with ethyl acetate
4. 4
   추출The organic extract
5. 5
   건조was dried over anhydrous magnesium sulfate
6. 6
   기타evaporated
7. 7
   기타to leave a dark red gum that
8. 8
   workup.STIRRINGthe mixture stirred overnight
9. 9
   기타The acetone was removed by evaporation
10. 10
    추출the aqueous solution extracted with dichloromethane
11. 11
    추출extracted with dichloromethane
12. 12
    건조dried over anhydrous magnesium sulfate
13. 13
    기타evaporated under reduced pressure
14. 14
    기타SCX purification (
15. 15
    세척eluting with methanol

실험 절차

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).

출처