To the reaction flask was added 100 g of deionized water and 20.0 g of 6-aminopenicillanic acid (6-APA) was slowly added under stirring conditions, after which the reaction system was cooled to 0-5 °C. Accurately weighed 10.6 g of sodium carbonate and dissolved in 100 mL of deionized water to prepare a 1 mol/L solution of sodium carbonate. Keeping the reaction temperature below 10 °C, the sodium carbonate solution was slowly added dropwise to the reaction flask to obtain an aqueous sodium salt solution of 6-APA. Next, 28.0 g of 3-(2-chloro-6-fluorophenyl)-5-methylisoxazole-4-carboxylic acid chloride was added to the reaction system and the addition time was controlled to be within 1 hour. The reaction system was stirred at 20~25°C for 4 hours. After completion of the reaction, the pH of the reaction solution was slowly adjusted to 2.5 with 1 mol/L dilute hydrochloric acid. 400 g of ethyl acetate was added to the reaction flask, and liquid-liquid partitioning was carried out after thorough stirring to separate the ethyl acetate phase. The ethyl acetate phase was washed sequentially with 200 g of saturated sodium chloride solution and then dried with 20 g of anhydrous sodium sulfate for 30 min to obtain an ethyl acetate solution of flucloxacillinic acid. A 1 mol/L solution of sodium isooctanoate was prepared by accurately weighing 18.0 g of sodium isooctanoate and dissolving it in 108 mL of ethyl acetate. This sodium isooctanoate solution was slowly added dropwise to the ethyl acetate solution of flucloxacillinic acid, and after the dropwise addition was completed, a white solid was gradually precipitated in the system. The reaction system was cooled to 5-10°C and crystallization was continued for 3 hours. The solid was collected by filtration, washed twice with ethyl acetate and subsequently dried under vacuum at 50 °C to obtain 41.3 g of flucloxacillin sodium monohydrate, the purity of the product was 99.8% as determined by HPLC and the yield was 90.6%.
