113-98-4

61-33-6

113-98-4

Synthesis of (2S,5R,6R)-3,3-dimethyl-7-oxo-6-(2-phenylacetamido)-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid as (2S,5R,6R)-3,3-dimethyl-7-oxo-6-(2-phenylacetamido)-4-thia-1-azabicyclo[3.2.0]heptane-2- Potassium carboxylate was performed in the following general steps: first, 1000 mL of the activated charcoal-treated extract (containing about 100,000 Oxford units of penicillin G/mL) was dissolved in n-butyl acetate. Subsequently, a 50% (w/w) aqueous solution of K2CO3 was added to this solution, ensuring that the molar amount of potassium in the mixture was about 1.0 equivalent of penicillin G. Next, a volume of liquid was evaporated by heating the mixture under vacuum using a rotary film evaporator (bath temperature 45-48°C) (see Table 1 for specific evaporation volumes). After evaporation was completed, methanol was added to the residue and stirred at 25°C for 1 hour. Afterwards, the suspension was filtered and the wet filter cake was washed with 70 mL of n-butyl acetate and finally the wet filter cake was dried. Table 1 details the total volume of evaporation and the volume of the aqueous layer in the distillate after the addition of penicillin G potassium salt to n-butyl acetate (values in parentheses), as well as the moisture content of the evaporated residue. All experiments yielded white penicillin G potassium crystals in high yields (defined as 100% relative to the penicillin content in the activated charcoal-treated extract) with limited loss of penicillin from the mother liquor. The penicillin G potassium content of the crystals obtained in Experiment 1 was 99.3%, indicating excellent quality of the crystals.