Diethyl acetamidomalonate (12.84 g, 59.11 mmol) was added to freshly prepared 0.29 M NaOEt (225 ml) in EtOH at 0° C. The solution resulting after brief sonication was transferred to an addition funnel and added over six minutes to a suspension of 20 (10.68 g, 53.74 mmol) in EtOH (50 ml) at 0° C. After stirring the reaction mixture for 18 hours at room temperature, solvent was removed in vacuo. Cold 0.25 N HCl (200 ml) was added and the aqueous phase was extracted with CHCl3 (200 ml, 2×100 ml). The organic layer was washed with H2O (100 ml). After solvent removal, the solid was purified by silica gel flash column chromatography using 4% acetone/-CH2Cl2 to furnish 18.1 g (89%) of diethyl (acetylamino)[3-(2-hydroxy-5-methylphenyl)-3-oxopropyl]propanedioate (I) as a solid: NMR δ 1.26 (t, 6H, J=7), 2.04 (s, 3H), 2.30 (s, 3H), 2.78 (t, 2H, J=7), 2.98 (t, 2H, J=7), 4.17-4.34 (m, 4H), 6.79 (s, 1H), 6.88 (d, 1H, J=8), 7.25-7.30 (m, 1H), 7.47 (s, 1H), 11.97 (s, 1H). Anal. calcd. for C19H25NO7 : C 60.15, H 6.64, N 3.69. Found: C 60.23, H 6.73, N 3.77.
