250 mL of dichloromethane was added to each of the four reaction flasks, and 20 g of methyl (7α,17α)-17-hydroxy-3-oxo-pregna-4,9(11)-dien-7,21-dicarboxylate-gamma-lactone (Compound 2), 48 g of trichloroacetamide, and 18 g of potassium acetate were added sequentially under stirring until complete dissolution. The reaction mixture was cooled to 10 °C and 160 mL of 30% hydrogen peroxide solution was slowly added dropwise for a controlled time of 45 minutes. After the dropwise addition, the reaction temperature was raised to 15 °C, the reaction was continued to be stirred, and the progress of the reaction was monitored by TLC until the disappearance of the raw material point. Upon completion of the reaction, layering was performed and the aqueous layer was extracted with dichloromethane (50 mL × 2). The organic layer was combined and washed sequentially with 3% sodium bisulfite solution (25 mL × 2), cold 1N NaOH solution, 3% dilute hydrochloric acid, water and saturated saline. The organic layer was dried by adding anhydrous Na2SO4 for 1 h. The desiccant was removed by filtration and the filtrate was concentrated to obtain a white solid. The resulting white solid was dissolved in 160 mL of butanone and stirred until completely dissolved. The solution was concentrated to 45% of the original volume under atmospheric pressure and the concentration was stopped. The solution was cooled naturally to 20°C, then cooled to 0°C with ice brine, kept for 1 hour and filtered, and the filter cake was washed with butanone. The filter cake was dried at 90 °C for 4 h to give 19.0 g (2'R,4aS,4bR,5aR,6aS,9aS,9bR,10R)-methyl 4a,6a-dimethyl-2,4'-dioxo-3,4,4a,4',5a,5',6,6a,8,9,9a,9b,10,11-tetradecanedihydro-2H,3'H-spiro[cyclopentadieno [1,2]phenanthro[4,4a-b]oxirane-7,2'-furan]-10-carboxylic acid ester (eplerenone), yield 91.3%, content 99.7%.
