Butanenitrile, 2-(ethoxymethylene)-3-oxo-, (Z)- (9CI) synthesis

Yield: 37%

Reaction Conditions:

with acetic anhydride at 130; for 2 h;Inert atmosphere;

Steps:

Compound 257.2. (Z)-2-(Ethoxymethylene)-3-oxobutanenitrile
Compound 257.2. (Z)-2-(Ethoxymethylene)-3-oxobutanenitrile.
Into a round- bottom flask, which was purged and maintained with an inert atmosphere of nitrogen, was placed a solution of 3-oxobutanenitrile (compound 257.1, 16.0 g, 193 mmol) in acetic anhydride (48 mL). Triethyl orthoformate (96 mL, 577 mmol) was added and the reaction was stirred for 2 h at 130 °C, then concentrated under reduced pressure to obtain the title compound as a red solid (10 g, 37%).

References:

3-V BIOSCIENCES, INC.;HEUER, Timothy Sean;OSLOB, Johan D.;MCDOWELL, Robert S.;JOHNSON, Russell;YANG, Hanbiao;EVANCHIK, Marc;ZAHARIA, Cristiana A.;CAI, Haiying;HU, Lily W. WO2015/95767, 2015, A1 Location in patent:Page/Page column 301