Acetamidomalonic acid diethyl ester → Diethyl acetamido[2-(2-nitrophenyl)ethyl]propanedioate

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Reaction Steps

A solution of diethyl acetamidomalonate (33.2 g) in ethanol (150 ml) was added to a solution of sodium ethoxide in ethanol [prepared from sodium (3.8 g) and ethanol (200 ml)]. The reaction mixture was stirred at room temperature for 30 minutes and a solution of 2-nitrophenethyl bromide (J. Med. Chem. 20, 1020 (1977), 40.0 g) in ethanol (100 ml) was added dropwise during 20 minutes. After addition was complete, the reaction mixture was refluxed for 18 hours, then cooled to room temperature and evaporated under reduced pressure. The residue was dissolved in water (350 ml) and the solution extracted with ethyl acetate (2×350 ml). The combined ethyl acetate extracts were washed with water (200 ml) and dried over magnesium sulfate. Removal of the solvent under reduced pressure gave diethyl 2-acetamido-2-(o-nitrophenethyl)malonate as a low melting solid, used without further purification for the next synthetic step.

Provenance & Evidence