Ethanol → Ethyl 3-oxo-3-(pyridin-2-yl)propanoate

Participants

Reaction Conditions

Reaction Steps

Stir a mixture of sodium ethoxide (360 g, 5.29 mol, 2 eq), toluene (4 L), ethanol (18 mL, 0.265 mol, 0.1 eq) and ethyl acetate (1.04 L, 10.58 mol, 4 eq) in a 22 L flask equipped with a reflux condenser, nitrogen inlet and mechanical stirrer. Stir for 1 h as the mixture warms to 26° C. Add pyridine-2-carboxylic acid ethyl ester (Fluka; 400 g, 2.65 mol, 1 eq) and heat the mixture to reflux (90° C.) for 18 h. Cool the mixture to room temperature. Dilute with toluene (8 L), wash with water (6 L), and separate the layers. Acidify the aqueous layer to pH 5 with glacial acetic acid. Extract with ethyl acetate (2×4 L), dry the combined organic layers (sodium sulfate), filter and concentrate in vacuo to yield the subtitled compound (466 g, 91% yield) as a dark oil in 93% purity by HPLC analysis. MS ES+ m/e 194 (M+1).

Provenance & Evidence