Réaction #1724936

Équation de réaction

Methyl magnesium bromide

ether

1-isoquinoline carbonitrile

→

1-acetylisoquinoline

Rendement 62.0%

Solvants

tetrahydrofuran

Conditions de réaction

Traitement

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

Mode opératoire

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.

Source