Water → Ampicillin

Participants

Reaction Steps

Tetrabutylammonium hydrogen sulfate (33.9 g, 0.10 mole) and 50 ml of 2N NaOH were combined with 200 ml H2O. The resulting pH was about 6.8. With stirring, CH2Cl2 (300 ml) and then ampicillin trihydrate (33.9 g, 0.10 mole) were added, and the pH adjusted from 4.5 to 8.5 with 53 ml 2N NaOH. The layers were separated and the aqueous layer extracted 4×200 ml CH2Cl2. The five organic layers were combined and evaporated to dryness in vacuo to yield the tetrabutylammonium salt of ampicillin, 54.1 g, 91.7%. Methyl acetoacetate (200 ml) was added to the salt and the water formed in the reaction removed by evaporation using a bath at 35° and a pressure of 5 mm. After one hour, title product began to crystallize. After 1.75 hour, 600 ml of ethyl acetate and 200 ml of hexane were added. After cooling to 0°-5°, title product was recovered by filtration, 53.5 g, 84.8% from salt, 77.8% overall from ampicillin; 1H-nmr (CDCl3) delta: 7.2 (m), 5.6-5.0 (m), 4.5 (s), 4.2 (s), 3.55 (s), 3.4-2.9 (m), 1.8 (s), 1.7-0.8 (m).

Provenance & Evidence