33279-01-5

A facile procedure for the high-yielding acylation of nitrile anions with unactivated esters to provide β-?keto nitriles (Propionylacetonitrile) is reported.

The general procedure for the synthesis of 3-oxopentanenitrile from ethyl propionate is as follows: - Acetonitrile (1.17 mL) was slowly added dropwise to a stirred n-butyllithium solution (1.6 M hexane solution, 14.06 mL) at -78 °C and stirred at this temperature for 1 hour. - Subsequently, ethyl propionate (1.5 mL) was added dropwise and the reaction mixture was slowly warmed to -45 °C, at which temperature stirring was continued for 2 hours. - Upon completion of the reaction, the mixture was acidified to pH 2 with aqueous 2N hydrochloric acid and then concentrated by evaporation. - The residue was extracted with dichloromethane and the combined organic phases were dried over magnesium sulfate, followed by evaporation of the solvent. - 3-Oxopentanenitrile was finally obtained in 80% yield. 1H NMR (CDCl3) δ: 1.14 (t, 3H), 2.66 (q, 2H), 3.46 (s, 2H).

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