Ampicillin → Penicillanic Acid

Participants

Reaction Conditions

Reaction Steps

2,3-Dimethyl-1-phenyl-3-pyrazolin-5-one-4-carboxylic acid (0.186 g, 0.8 mmol) in dry dimethyl formamide (D.M.F) (4 ml) was treated with triethylamine (0.12 ml, 0.8 mmol). The solution was cooled to -10° C. and isobutyl chloroformate (0.10 ml, 0.76 mmol) added dropwise. After 1 hour at -10° C., solids were removed by filtration and the solution added to ampicillin (anhydrous) (0.28 g, 0.8 mmol) premixed with triethylamine (0.12 ml, 0.8 mmol) in D.M.F. (10 ml) at -40° C. The solution was allowed to warm to 0° C., stirred for 90 minutes and poured into excess dry ether, with stirring. The precipitate was isolated and partitioned between ethyl acetate and water. The pH was adjusted to 7.5 (bicarbonate addition); the aqueous layer separated and acidified to pH 1.5 (HCl(5N)). Extraction with ethyl acetate, drying (Na2SO4) and evaporation gave the title product as the free penicillanic acid (0.09 g, 20%), δ((CD3)2CO) 1.50, 1.58 (2×3H, 2s, (CH3)2), 2.68 (3H, s,=C--CH3), 3.34 (3H, s, --NCH3), 4.36 (1H, s, C3 -proton), 5.53 (1H, d, J 4 Hz, C5 -proton), 5.71 (1H, d of d, J 4, 8 Hz, C6 -proton), 5.94 (1H, d, J 8 Hz, --CHCON--), 7.53 (10H, complex, aryl protons), 8.20 (1H, d, J 8 Hz, --NH--), 9.78 (1H, d, J 8 Hz, --NH--), 6.5-9 (1H, br, --CO2H). The free acid was converted to the sodium salt by addition, to an acetone solution of the free acid, of a solution of sodium ethylhexanoate (0.084 ml, 1.9N) in methyl isobutyl ketone, further addition of ether, and filtration of the precipitate. The sodium salt (2) showed vmax (nujol) 1780, 1760, 1690, 1655, 1600 cm-1.

Provenance & Evidence