반응 #1724936

반응 방정식

Methyl magnesium bromide

ether

1-isoquinoline carbonitrile

→

1-acetylisoquinoline

수율 62.0%

용매

tetrahydrofuran

반응 조건

후처리

1. 1
   건조dried 100 ml two neck round bottom flask under nitrogen
2. 2
   workup.ADDITIONis diluted with 8 ml diethyl ether
3. 3
   온도The reaction is warmed
4. 4
   온도to reflux for one hour
5. 5
   온도is cooled to 0° C.
6. 6
   기타is quenched with 20 ml 6 M hydrochloric acid
7. 7
   온도The reaction mixture is warmed to 50° C. for two hours
8. 8
   온도is cooled
9. 9
   workup.ADDITIONis poured into 75 ml 2N sodium hydroxide
10. 10
    추출The mixture is extracted with 3×80 ml ethyl acetate
11. 11
    건조the combined organics are dried over potassium carbonate
12. 12
    농축The dried organics are concentrated in vacuo to a crude amber oil
13. 13
    기타The crude material is chromatographed over 150 g silica gel (230-400 mesh)
14. 14
    세척eluting with 10% acetone/hexane
15. 15
    기타while collecting 22 ml fractions
16. 16
    농축concentrated

실험 절차

Methyl magnesium bromide in ether (8.1 ml, 24.3 mmole) is dissolved in 16 ml tetrahydrofuran in an oven dried 100 ml two neck round bottom flask under nitrogen. The solution is cooled to 0° C., is diluted with 8 ml diethyl ether, and is treated with 1-isoquinoline carbonitrile (3.0 g, 19.5 mmole). The reaction is warmed to reflux for one hour, is cooled to 0° C., and is quenched with 20 ml 6 M hydrochloric acid. The reaction mixture is warmed to 50° C. for two hours, is cooled, and is poured into 75 ml 2N sodium hydroxide. The mixture is extracted with 3×80 ml ethyl acetate and the combined organics are dried over potassium carbonate. The dried organics are concentrated in vacuo to a crude amber oil. The crude material is chromatographed over 150 g silica gel (230-400 mesh), eluting with 10% acetone/hexane, while collecting 22 ml fractions. Fractions 16-26 are combined and concentrated to provide 2.1 g (62%) of 1-acetylisoquinoline.

출처