Acetone → Penicillanic Acid

Participants

Reaction Conditions

Reaction Steps

Sodium 6,7,8,9-tetrahydro-4-oxo-4H-pyrido-[1,2-a]pyrimidine-3-carboxylate (2mM, 0.432g.) was suspended in a mixture of dry acetone (25ml) and dry dimethylacetamide (2ml) and chilled to -10° C with stirring. Ethyl chloroformate (2mM, 0.2ml) and one drop of N-methyl morpholine were added and the reaction mixture stirred 20 minutes at -10° C. A solution of ampicillin trihydrate (2mM, 0.726g) in aqueous sodium hydroxide (0.489N, 3.64ml) was chilled and added to the mixed anhydride at -10° C. The reaction was stirred 1.75 hours to ambient temperature, the acetone evaporated, and the resulting solution diluted to 100ml with water, covered with ethyl acetate (50ml) and adjusted to pH 2.0 with 5N HCl. The organic layer was separated, the aqueous phase extracted with ethyl acetate (1 × 50ml), the organic extracts combined, washed with water (3 × 30ml), dried over magnesium sulphate to give the penicillanic acid as a white solid 0.85g. (85%), showing a single component on t.l.c., Rf 0.51 (chloroform/acetone/acetic acid; 7:7:1) δ [(CD3)2SO] 1.4, 1.55 (6H, 2 × s, gem dimethyls), 1.7 ##STR54## 4.17 (1H, s, C3 proton), 5.3 - 5.6 (2H, m, β-lactam protons), 5.87 (1H, d, α-proton), 7.1 - 7.5 (5H, m, aromatics), 8.5 (1H, s, pyrimidine proton), 9.2 - 10.0 (2H, 2 × d, 2 × NH); λmax (0.3% NaHCO3 solution) 206 (ε = 25,800), 230 (ε = 12,140) and 300 n.m. (ε = 11,000).

Provenance & Evidence