Step A: Synthesis of ethyl 3-hydroxy-3-methylbutyrate: lithium bis(trimethylmethylsilyl)amide (1M THF solution, 100 mL, 100 mmol) was dissolved in tetrahydrofuran (100 mL) under nitrogen protection and cooled to -78 °C. Ethyl acetate (9.74 mL, 100 mmol) was slowly added and the reaction mixture was stirred at this temperature for 30 minutes. Subsequently, acetone (8.81 mL, 120 mmol) was added and stirring was continued for 10 minutes. Upon completion of the reaction, the reaction was quenched with 2M aqueous hydrochloric acid (70 mL, 140 mmol) and gradually warmed to room temperature. The reaction mixture was extracted with ethyl acetate (2×150 mL), and the organic phases were combined, washed sequentially with saturated aqueous sodium bicarbonate (2×50 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to afford the yellow oily target product ethyl 3-hydroxy-3-methylbutyrate (12.8 g, 88% yield). The product was characterized by 1H NMR (CDCl3): δ 4.18 (q, 3H), 2.49 (s, 2H), 1.29 (m, 9H).
