Diethyl Ether → 1-(Isoquinolin-1-yl)ethan-1-one

Temperature

0 °C

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.

1. dry with materialdried 100 ml two neck round bottom flask under nitrogen
2. additionis diluted with 8 ml diethyl ether
3. temperatureThe reaction is warmed
4. temperatureto reflux for one hour
5. temperatureis cooled to 0° C.
6. customis quenched with 20 ml 6 M hydrochloric acid
7. temperatureThe reaction mixture is warmed to 50° C. for two hours
8. temperatureis cooled
9. additionis poured into 75 ml 2N sodium hydroxide
10. extractionThe mixture is extracted with 3×80 ml ethyl acetate
11. dry with materialthe combined organics are dried over potassium carbonate
12. concentrationThe dried organics are concentrated in vacuo to a crude amber oil
13. customThe crude material is chromatographed over 150 g silica gel (230-400 mesh)
14. washeluting with 10% acetone/hexane
15. customwhile collecting 22 ml fractions
16. concentrationconcentrated

ORD record

ord-09329fcf14b84744a898443ecf5a5188

Source dataset

uspto-grants-2000_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06043248