Diethyl Malonate → 2-(N-tert-butoxycarbonyl-4-butylamino)malonic acid diethyl ester

Participants

Reaction Conditions

Reaction Steps

Metallic sodium (0.28 g, 0.012 mol) is dissolved in absolute ethyl alcohol (EtOH) (9 ml) under nitrogen atmosphere. The mixture is heated to 60° C. and diethyl malonate (3.8 g, 0.024 mol) is then dripped therein. N-tert-butoxycarbonyl-4-chloro-butylamine (2.5 g, 0.012 mol) is then gradually added, at room temperature, to the resulting solution. The reaction mixture is stirred at room temperature for 2 hours and at the reflux temperature for 6 hours, and then poured into a mixture AcOEt/water (100 ml 1/1 v/v). The organic phase which is separated is then washed repeatedly with water and dried over MgSO4The solvent is removed under vacuum at 100° C. affording a crude oily product which is purified by reverse-phase HPLC on an RP-18 column eluting with an aqueous phase modified with CH3CN (45% by volume). The desired compound (1.31 g) is thus obtained as a pure product.

Provenance & Evidence